Endothelial cell population dynamics in rat brain after local irradiation

Ljubimova, N. V.; Levitman, M. Kh.; Plotnikova, E.; Eidus, L.Kh.

doi:10.1259/0007-1285-64-766-934

Cited by 101 publications

(66 citation statements)

References 8 publications

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“…Further studies are warranted to determine whether changes in gait after WBI correlate with the severity of post-radiation cerebromicrovascular deficits. Previous studies by us and others have shown that WBI also results in a significant microvascular rarefaction (Ljubimova et al 1991;Warrington et al 2012), particularly in the hippocampus, the region responsible for spatial learning and memory (Warrington et al 2011). It is likely that neurovascular uncoupling and microvascular rarefaction act synergistically to impair regional blood supply in the brain (Fuss et al 2000;Taki et al 2002), exacerbating cognitive decline.…”

Section: Discussionmentioning

confidence: 93%

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

et al. 2017

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Whole brain irradiation (WBI) is a mainstream therapy for patients with both identifiable brain metastases and prophylaxis for microscopic malignancies. However, it also promotes accelerated senescence in healthy tissues and leads to progressive cognitive dysfunction in up to 50% of tumor patients surviving long term after treatment, due to γ-irradiation-induced cerebromicrovascular injury. Moment-to-moment adjustment of cerebral blood flow ( C B F ) v i a n e u r o n a l a c t i v i t y -d e p e n d e n t cerebromicrovascular dilation (functional hyperemia) has a critical role in maintenance of healthy cognitive function. To determine whether cognitive decline induced by WBI associates with impaired cerebromicrovascular function, C56BL/6 mice (3 months) subjected to a clinically relevant protocol of fractionated WBI (5 Gy twice weekly for 4 weeks) and control mice were compared. Mice were tested for spatial memory performance (radial arm water maze), sensorimotor coordination (computerized gait analysis, CatWalk), and cerebromicrovascular function (whisker-stimulation-induced increases in CBF, measured by laser Doppler flowmetry) at 3 to 6 months post-irradiation. We found that mice with WBI exhibited impaired cerebromicrovascular function at 3 months post-irradiation, which was associated with impaired performance in the radial arm water maze. At 6 months, post-irradiation progressive impairment in gait coordination (including changes in the regularity index and phase dispersion) was also evident. Collectively, our findings provide evidence for early and persisting neurovascular impairment after a clinically relevant protocol of fractionated WBI, which predict early manifestations of cognitive impairment.

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Section: Discussionmentioning

confidence: 93%

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

et al. 2017

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“…In an animal model, after receiving 5-200 Gy radiation, approximately 15 % of endothelia are lost within 24 h followed by continued endothelial loss that lasts for months [3]. Apoptosis contributes this process in a dose-dependent fashion [4] and is mediated by acid sphingomyelinase [5].…”

Section: Introductionmentioning

confidence: 99%

Review of cranial radiotherapy-induced vasculopathy

et al. 2015

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Cranial radiation can impact the cerebral vasculature in many ways, with a wide range of clinical manifestations. The incidence of these late effects including cerebrovascular accidents (CVAs), lacunar lesions, vascular occlusive disease including moyamoya syndrome, vascular malformations, and hemorrhage is not well known. This article reviews the preclinical findings regarding the pathophysiology of late radiation-induced vascular damage, and discusses the clinical incidence and risk factors for each type of vasculopathy. The pathophysiology is complex and dependent on the targeted blood vessels, and upregulation of pro-inflammatory and hypoxia-related genes. The risk factors for adult CVAs are similar to those for patients not exposed to cranial radiotherapy. For children, risks for late vascular complications include young age at radiotherapy, radiotherapy dose, NF1, tumor location, chemotherapy, and endocrine abnormalities. The incidence of late vascular complications of radiotherapy may be impacted by improved technology, therapeutic interventions, and appropriate follow up.

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“…Considerably fewer studies have investigated the effects of irradiation on the young, developing brain and very little is known about how microvessels in the hippocampus respond to this type of insult. [17][18][19] Therefore, the primary aim of this study was to investigate how microvessels in the hippocampus were affected by irradiation to the young mouse brain, by quantifying blood vessel parameters at different time points after irradiation. We also sought to investigate the role of the neurovascular niche in the support and survival of neural stem/progenitor cells.…”

Section: Introductionmentioning

confidence: 99%

Irradiation to the Young Mouse Brain Caused Long-Term, Progressive Depletion of Neurogenesis but did not Disrupt the Neurovascular Niche

Boström

Kalm

Karlsson

et al. 2013

J Cereb Blood Flow Metab

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We investigated the effects of ionizing radiation on microvessel structure and complexity in the hippocampus. We also assessed neurogenesis and the neurovascular niche. Postnatal day 14 male C57BL/6 mice received a single dose of 8 Gy to the whole brain and were killed 6 hours, 1 week, 7 weeks, or 1 year later. Irradiation decreased the total number of microvessels and branching points from 1 week onwards and decreased the total microvessel area 1 and 7 weeks after irradiation. After an initial increase in vascular parameter densities, concomitant with reduced growth of the hippocampus, the densities normalized with time, presumably adapting to the needs of the surrounding nonvascular tissue. Irradiation decreased the number of neural stem and progenitor cells in the hippocampus. The relative loss increased with time, resulting in almost completely ablated neurogenesis (DCX þ cells) 1 year after irradiation (77% decreased 1 week, 86% decreased 7 weeks, and 98% decreased 1 year after irradiation compared with controls). After irradiation, the distance between undifferentiated stem cells and microvessels was unaffected, and very few dying endothelial cells were detected. Taken together, these results indicate that the vasculature adjusts to the surrounding neural and glial tissue after irradiation, not vice-versa.

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Endothelial cell population dynamics in rat brain after local irradiation

Cited by 101 publications

References 8 publications

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

Review of cranial radiotherapy-induced vasculopathy

Irradiation to the Young Mouse Brain Caused Long-Term, Progressive Depletion of Neurogenesis but did not Disrupt the Neurovascular Niche

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