Changes in regional cerebral blood flow in irradiated regions and normal brain after stereotactic radiosurgery

Taki, Suzuka; Higashi, Kõtarõ; Oguchi, Manabu; Tamamura, Hiroyasu; Tsuji, Shiro; Ohta, Kiyotaka; Tonami, Hisao; Yamamoto, Ikuo; Okamoto, Kazuya; Iizuka, Hideaki

doi:10.1007/bf03000106

Cited by 25 publications

(21 citation statements)

References 10 publications

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“…Decreased glucose metabolism in the radiation-injured or peri-radiation-injured brain tissue [46] and in brain regions receiving over 40 Gy radiation [47] has also been reported. Similar decreases in cerebral blood flow were observed in the targeted and surrounding healthy tissue weeks following stereotaxic radiosurgery [48]. These studies illustrate that radiation therapy induces a long-term reduction in vascular density that is followed by decreased cerebral blood flow and metabolism.…”

Section: Vasculature Effects Of Wbrtsupporting

confidence: 59%

Whole Brain Radiation-Induced Vascular Cognitive Impairment: Mechanisms and Implications

Warrington

Ashpole

Csiszár³

et al. 2013

J Vasc Res

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Mild cognitive impairment is a well-documented consequence of whole brain radiation therapy (WBRT) that affects 40-50% of long-term brain tumor survivors. The exact mechanisms for the decline in cognitive function after WBRT remain elusive and no treatment or preventative measures are available for use in the clinic. Here, we review recent findings indicating how changes in the neurovascular unit may contribute to the impairments in learning and memory. In addition to affecting neuronal development, WBRT induces profound capillary rarefaction within the hippocampus - a region of the brain important for learning and memory. Therapeutic strategies such as hypoxia, which restore the capillary density, result in the rescue of cognitive function. In addition to decreasing vascular density, WBRT impairs vasculogenesis and/or angiogenesis, which may also contribute to radiation-induced cognitive decline. Further studies aimed at uncovering the specific mechanisms underlying these WBRT-induced changes in the cerebrovasculature are essential for developing therapies to mitigate the deleterious effects of WBRT on cognitive function.

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Section: Vasculature Effects Of Wbrtsupporting

confidence: 59%

Whole Brain Radiation-Induced Vascular Cognitive Impairment: Mechanisms and Implications

Warrington

Ashpole

Csiszár³

et al. 2013

J Vasc Res

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“…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. It is important that both neurovascular dysfunction and microvascular rarefaction are manifested relatively early (within 3 months) after WBI and their onset coincides with the appearance of cognitive symptoms.…”

Section: Discussionmentioning

confidence: 94%

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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“…39 However, in a recent study on 13 patients, a reduction of regional CBF at 2 weeks and 3 months after stereotactic radiosurgery in out-of-field areas (Ͻ5 Gy) was observed by 99m Tc-HMPAO scintigraphy. 58 High precision stereotactic radiosurgery is used to deliver high doses of radiation to small intracranial tumors, while the dose to surrounding normal brain tissue is minimized due to the steep radiation dosage decline at the border of the target volume. 5,8 In our study, the normal brain parenchyma examined was only affected by radiation doses less than 0.5 Gy, 38 which might explain the conflicting results.…”

Section: Investigative Radiology • Volume 39 Number 5 May 2004mentioning

confidence: 99%

Assessment of Irradiated Brain Metastases by Means of Arterial Spin-Labeling and Dynamic Susceptibility-Weighted Contrast-Enhanced Perfusion MRI

Weber

Thilmann

Lichy

et al. 2004

Investigative Radiology

102

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Changes in regional cerebral blood flow in irradiated regions and normal brain after stereotactic radiosurgery

Abstract: These results suggest that subclinical regional CBF reduction occurs after SRS in the normal brain in out-of-field of radiation.

Cited by 25 publications

References 10 publications

Whole Brain Radiation-Induced Vascular Cognitive Impairment: Mechanisms and Implications

Whole Brain Radiation-Induced Vascular Cognitive Impairment: Mechanisms and Implications

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

Assessment of Irradiated Brain Metastases by Means of Arterial Spin-Labeling and Dynamic Susceptibility-Weighted Contrast-Enhanced Perfusion MRI

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