Metabolic and histopathological changes in the brain and plasma of rats exposed to fractionated whole-brain irradiation

Objective: To evaluate the efficiency of high-energy photons for mitigating alopecia due to whole-brain irradiation (WBRT). Methods: Planning CT data from 10 patients who received WBRT were collected. We prepared 4 WBRT plans that used 6 or 15 MV photon beams, with or without use of a field-in-field (FiF) technique, and compared outcomes using a treatment planning system. The primary outcome was dose parameters to the scalp, including the mean dose, maximum dose, and dose received to 50% scalp (D50%). Secondary outcomes were minimum dose to the brain surface. Results: Using FiF, the mean doses were 24.4–26.0 and 22.4–24.1 Gy, and the maximum doses were 30.5–32.1 and 28.5–30.8 Gy for 6 and 15 MV photon beams, respectively. Without FiF, the mean doses were 24.6–26.9 and 22.6–24.5 Gy, and the maximum doses were 30.8–34.6 and 28.6–32.4 Gy for 6 and 15 MV photon beams. The 15 MV plan resulted in a lower scalp dose for each dose parameter (p < 0.001). Using FiF, the minimum doses to the brain surface for the 6 and 15 MV plans were 28.9 ± 0.440 and 29.0 ± 0.557 Gy, respectively (p = 0.70). Without FiF, the minimum doses to the brain surface for the 6 and 15 MV plans were 28.9 ± 0.456 and 29.0 ± 0.529, respectively (p = 0.66). Conclusion: Compared with the 6 MV plan, the 15 MV plan achieved a lower scalp dose without impairing the brain surface dose. Advances in knowledge: High-energy photon WBRT may mitigate alopecia of patients who receiving WBRT.

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Chemotherapy for patients with brain metastases from melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e19012 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e19012-e19012

Author(s):

David R. Naskhletashvili ◽

Vera A. Gorbunova ◽

Mark B. Bychkov ◽

Ali H. Bekyashev ◽

Vladislav B. Karahan ◽

...

Keyword(s):

Partial Response ◽

Brain Metastases ◽

Metastatic Melanoma ◽

Objective Response ◽

Complete Response ◽

Combined Chemotherapy ◽

Whole Brain Irradiation ◽

Whole Brain ◽

Brain Irradiation ◽

The Brain

e19012 Background: There have not been standards of chemo- and chemo-radiotherapy for treatment for patients with brain metastases. The patients (pts) with brain metastases (BM) from melanoma have poor prognoses. The main goal of this trial is to assess the efficacy of nitrosoureas (CCNU or FCNU), temozolomide (TMZ) as monotherapy, TMZ combined with whole brain irradiation (WBI), or combined chemotherapy of TMZ and cisplatin in pts with BM from melanoma. Methods: 78 pts were included in this study. 21 pts were treated with WBI (3Gy/30Gy) and concomitant TMZ therapy (75 mg/m2/day orally on days 1-14), 19 pts were treated with TMZ (150 mg/m2/day orally on days 1-5, every 4 weeks) as monotherapy, 17 pts pts were treated with nitrosoureas (CCNU or FCNU), 21 pts were treated with combined chemotherapy of TMZ (150/mg/m2/day orally on days 1-5, every 4 weeks) + cisplatin (20/mg/m2/day intravenous on days 1-5, every 4 weeks). The main aims of this study were objective response (OR) – complete response (CR) + partial response (PR) in the brain and in the extracranial sites (ES), median of survival (mOS), 1-year and 2-year survival. Results: Observations were as follows: in the TMZ + WBI treated pts, 4 OR (19,0%) in 21 pts group in the brain and 1 OR (6,7%) in 15 pts group in ES. The mOS was 6.0 months, 1-year survival was 23,8%. In the TMZ monotherapy treated pts there were 5 OR (26,3%) in 19 pts group in the brain and no OR in 13 pts group in ES. The mOS was 6 months, 1-year survival was 21,1%. In the nitrisoureas treated pts we achieved 2 OR (11,8%) in 17 pts group in the brain and 1 OR (9,1%) in 11 pts group in ES. The mOS was 5 months, 1-year survival was 17,6%. In the TMZ + cisplatin treated pts there were 7 OR (33.3%) in 21 pts group in the brain and 7 OR (35,0%) in 20 pts group in ES. The mOS was 8 months, 1-year survival was 33,3%. 2-year survival (19,0%) was achieved only in TMZ and cisplatin group. Conclusions: Previous results of our study showed promising higher efficacy of TMZ and cisplatin, especially in OR in ES (p<0.05) and in 2-year survival (p<0.05), in comparison with TMZ alone, nitrosoureas or TMZ with whole brain irradiation in patients with metastatic melanoma with BM. Control of extracranial lesions is important factor for patients with BM. Further investigation is to be expected.

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Effect of whole-brain irradiation on the specific brain regions in a rat model: Metabolic and histopathological changes

NeuroToxicology ◽

10.1016/j.neuro.2017.03.005 ◽

2017 ◽

Vol 60 ◽

pp. 70-81 ◽

Cited By ~ 12

Author(s):

Soňa Bálentová ◽

Petra Hnilicová ◽

Dagmar Kalenská ◽

Peter Murín ◽

Eva Hajtmanová ◽

...

Keyword(s):

Rat Model ◽

Brain Regions ◽

Histopathological Changes ◽

Whole Brain Irradiation ◽

Whole Brain ◽

Brain Irradiation

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

Neuro-Oncology ◽

10.1093/neuonc/noz175.342 ◽

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.

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Replacement of microglia by monocyte-derived macrophages prevents long-term memory deficits after therapeutic irradiation

10.1101/794354 ◽

2019 ◽

Cited By ~ 1

Author(s):

Xi Feng ◽

David Chen ◽

Sonali Gupta ◽

Sharon Liu ◽

Nalin Gupta ◽

...

Keyword(s):

Memory Deficits ◽

Intermediate Phenotype ◽

Long Term Memory ◽

Protective Effects ◽

Whole Brain Irradiation ◽

Whole Brain ◽

Brain Irradiation ◽

Brain Radiotherapy ◽

Therapeutic Irradiation ◽

The Brain

AbstractResident microglia of the brain have a distinct origin compared to macrophages in other organs. Under physiological conditions, microglia are maintained by self-renewal from the local pool, independent of hematopoietic progenitors. Pharmacologic depletion of microglia during therapeutic whole-brain irradiation prevents synaptic loss and rescues recognition memory deficits but the mechanisms behind these protective effects are unknown. Here we demonstrate that after a combination of therapeutic whole-brain irradiation and microglia depletion, macrophages originating from circulating monocytes engraft into the brain and replace the microglia pool. Comparisons of transcriptomes reveal that brain-engrafted macrophages have an intermediate phenotype that resembles both monocytes and embryonic microglia. Importantly, the brain-engrafted macrophages have a reduced phagocytic activity for synaptic compartments compared to the activated microglia from irradiated brains, which in turn prevent the aberrant and chronic synapse loss that results in radiation-induced memory deficits. These results are the first to demonstrate that replacement of microglia by brain-engrafted macrophages represent a potential therapeutic avenue for the treatment of brain radiotherapy induced cognitive deficits.

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Effect of fractionated whole-brain irradiation on brain and plasma in a rat model: Metabolic, volumetric and histopathological changes

Neurochemistry International ◽

10.1016/j.neuint.2021.104985 ◽

2021 ◽

Vol 145 ◽

pp. 104985

Author(s):

Soňa Bálentová ◽

Petra Hnilicová ◽

Dagmar Kalenská ◽

Eva Baranovičová ◽

Peter Muríň ◽

...

Keyword(s):

Rat Model ◽

Histopathological Changes ◽

Whole Brain Irradiation ◽

Whole Brain ◽

Brain Irradiation

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

Neuro-Oncology ◽

10.1093/neuonc/noz175.1145 ◽

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.

Download Full-text