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

Abstract 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 p...
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Autor*in:	Ungvari, Zoltan [verfasserIn] Tarantini, Stefano [verfasserIn] Hertelendy, Peter [verfasserIn] Valcarcel-Ares, M. Noa [verfasserIn] Fülöp, Gabor A. [verfasserIn] Logan, Sreemathi [verfasserIn] Kiss, Tamas [verfasserIn] Farkas, Eszter [verfasserIn] Csiszar, Anna [verfasserIn] Yabluchanskiy, Andriy [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	Whole brain irradiation Neurovascular coupling Functional hyperemia Dementia Gait dysfunction Neurovascular unit Cellular senescence DNA damage

Übergeordnetes Werk:	Enthalten in: Age - New York, NY : Springer Science+Business Media, 1978, 39(2017), 1 vom: Feb., Seite 33-42
Übergeordnetes Werk:	volume:39 ; year:2017 ; number:1 ; month:02 ; pages:33-42

Links:	Volltext

DOI / URN:	10.1007/s11357-017-9964-z

Katalog-ID:	SPR018906370

Internformat


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520			\|a Abstract 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 (CBF) via neuronal activity-dependent 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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allfields	10.1007/s11357-017-9964-z doi (DE-627)SPR018906370 (SPR)s11357-017-9964-z-e DE-627 ger DE-627 rakwb eng 610 ASE 44.68 bkl Ungvari, Zoltan verfasserin aut Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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 (CBF) via neuronal activity-dependent 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. Whole brain irradiation (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Functional hyperemia (dpeaa)DE-He213 Dementia (dpeaa)DE-He213 Gait dysfunction (dpeaa)DE-He213 Neurovascular unit (dpeaa)DE-He213 Cellular senescence (dpeaa)DE-He213 DNA damage (dpeaa)DE-He213 Tarantini, Stefano verfasserin aut Hertelendy, Peter verfasserin aut Valcarcel-Ares, M. Noa verfasserin aut Fülöp, Gabor A. verfasserin aut Logan, Sreemathi verfasserin aut Kiss, Tamas verfasserin aut Farkas, Eszter verfasserin aut Csiszar, Anna verfasserin aut Yabluchanskiy, Andriy verfasserin aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 39(2017), 1 vom: Feb., Seite 33-42 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:39 year:2017 number:1 month:02 pages:33-42 https://dx.doi.org/10.1007/s11357-017-9964-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4126 44.68 ASE AR 39 2017 1 02 33-42
spelling	10.1007/s11357-017-9964-z doi (DE-627)SPR018906370 (SPR)s11357-017-9964-z-e DE-627 ger DE-627 rakwb eng 610 ASE 44.68 bkl Ungvari, Zoltan verfasserin aut Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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 (CBF) via neuronal activity-dependent 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. Whole brain irradiation (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Functional hyperemia (dpeaa)DE-He213 Dementia (dpeaa)DE-He213 Gait dysfunction (dpeaa)DE-He213 Neurovascular unit (dpeaa)DE-He213 Cellular senescence (dpeaa)DE-He213 DNA damage (dpeaa)DE-He213 Tarantini, Stefano verfasserin aut Hertelendy, Peter verfasserin aut Valcarcel-Ares, M. Noa verfasserin aut Fülöp, Gabor A. verfasserin aut Logan, Sreemathi verfasserin aut Kiss, Tamas verfasserin aut Farkas, Eszter verfasserin aut Csiszar, Anna verfasserin aut Yabluchanskiy, Andriy verfasserin aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 39(2017), 1 vom: Feb., Seite 33-42 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:39 year:2017 number:1 month:02 pages:33-42 https://dx.doi.org/10.1007/s11357-017-9964-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4126 44.68 ASE AR 39 2017 1 02 33-42
allfields_unstemmed	10.1007/s11357-017-9964-z doi (DE-627)SPR018906370 (SPR)s11357-017-9964-z-e DE-627 ger DE-627 rakwb eng 610 ASE 44.68 bkl Ungvari, Zoltan verfasserin aut Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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 (CBF) via neuronal activity-dependent 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. Whole brain irradiation (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Functional hyperemia (dpeaa)DE-He213 Dementia (dpeaa)DE-He213 Gait dysfunction (dpeaa)DE-He213 Neurovascular unit (dpeaa)DE-He213 Cellular senescence (dpeaa)DE-He213 DNA damage (dpeaa)DE-He213 Tarantini, Stefano verfasserin aut Hertelendy, Peter verfasserin aut Valcarcel-Ares, M. Noa verfasserin aut Fülöp, Gabor A. verfasserin aut Logan, Sreemathi verfasserin aut Kiss, Tamas verfasserin aut Farkas, Eszter verfasserin aut Csiszar, Anna verfasserin aut Yabluchanskiy, Andriy verfasserin aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 39(2017), 1 vom: Feb., Seite 33-42 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:39 year:2017 number:1 month:02 pages:33-42 https://dx.doi.org/10.1007/s11357-017-9964-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4126 44.68 ASE AR 39 2017 1 02 33-42
allfieldsGer	10.1007/s11357-017-9964-z doi (DE-627)SPR018906370 (SPR)s11357-017-9964-z-e DE-627 ger DE-627 rakwb eng 610 ASE 44.68 bkl Ungvari, Zoltan verfasserin aut Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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 (CBF) via neuronal activity-dependent 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. Whole brain irradiation (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Functional hyperemia (dpeaa)DE-He213 Dementia (dpeaa)DE-He213 Gait dysfunction (dpeaa)DE-He213 Neurovascular unit (dpeaa)DE-He213 Cellular senescence (dpeaa)DE-He213 DNA damage (dpeaa)DE-He213 Tarantini, Stefano verfasserin aut Hertelendy, Peter verfasserin aut Valcarcel-Ares, M. Noa verfasserin aut Fülöp, Gabor A. verfasserin aut Logan, Sreemathi verfasserin aut Kiss, Tamas verfasserin aut Farkas, Eszter verfasserin aut Csiszar, Anna verfasserin aut Yabluchanskiy, Andriy verfasserin aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 39(2017), 1 vom: Feb., Seite 33-42 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:39 year:2017 number:1 month:02 pages:33-42 https://dx.doi.org/10.1007/s11357-017-9964-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4126 44.68 ASE AR 39 2017 1 02 33-42
allfieldsSound	10.1007/s11357-017-9964-z doi (DE-627)SPR018906370 (SPR)s11357-017-9964-z-e DE-627 ger DE-627 rakwb eng 610 ASE 44.68 bkl Ungvari, Zoltan verfasserin aut Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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 (CBF) via neuronal activity-dependent 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. Whole brain irradiation (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Functional hyperemia (dpeaa)DE-He213 Dementia (dpeaa)DE-He213 Gait dysfunction (dpeaa)DE-He213 Neurovascular unit (dpeaa)DE-He213 Cellular senescence (dpeaa)DE-He213 DNA damage (dpeaa)DE-He213 Tarantini, Stefano verfasserin aut Hertelendy, Peter verfasserin aut Valcarcel-Ares, M. Noa verfasserin aut Fülöp, Gabor A. verfasserin aut Logan, Sreemathi verfasserin aut Kiss, Tamas verfasserin aut Farkas, Eszter verfasserin aut Csiszar, Anna verfasserin aut Yabluchanskiy, Andriy verfasserin aut Enthalten in Age New York, NY : Springer Science+Business Media, 1978 39(2017), 1 vom: Feb., Seite 33-42 (DE-627)499546180 (DE-600)2201958-3 1574-4647 nnns volume:39 year:2017 number:1 month:02 pages:33-42 https://dx.doi.org/10.1007/s11357-017-9964-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_40 GBV_ILN_60 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_110 GBV_ILN_120 GBV_ILN_161 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_647 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4126 44.68 ASE AR 39 2017 1 02 33-42
language	English
source	Enthalten in Age 39(2017), 1 vom: Feb., Seite 33-42 volume:39 year:2017 number:1 month:02 pages:33-42
sourceStr	Enthalten in Age 39(2017), 1 vom: Feb., Seite 33-42 volume:39 year:2017 number:1 month:02 pages:33-42
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Whole brain irradiation Neurovascular coupling Functional hyperemia Dementia Gait dysfunction Neurovascular unit Cellular senescence DNA damage
dewey-raw	610
isfreeaccess_bool	false
container_title	Age
authorswithroles_txt_mv	Ungvari, Zoltan @@aut@@ Tarantini, Stefano @@aut@@ Hertelendy, Peter @@aut@@ Valcarcel-Ares, M. Noa @@aut@@ Fülöp, Gabor A. @@aut@@ Logan, Sreemathi @@aut@@ Kiss, Tamas @@aut@@ Farkas, Eszter @@aut@@ Csiszar, Anna @@aut@@ Yabluchanskiy, Andriy @@aut@@
publishDateDaySort_date	2017-02-01T00:00:00Z
hierarchy_top_id	499546180
dewey-sort	3610
id	SPR018906370
language_de	englisch
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author	Ungvari, Zoltan
spellingShingle	Ungvari, Zoltan ddc 610 bkl 44.68 misc Whole brain irradiation misc Neurovascular coupling misc Functional hyperemia misc Dementia misc Gait dysfunction misc Neurovascular unit misc Cellular senescence misc DNA damage Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence
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topic_title	610 ASE 44.68 bkl Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence Whole brain irradiation (dpeaa)DE-He213 Neurovascular coupling (dpeaa)DE-He213 Functional hyperemia (dpeaa)DE-He213 Dementia (dpeaa)DE-He213 Gait dysfunction (dpeaa)DE-He213 Neurovascular unit (dpeaa)DE-He213 Cellular senescence (dpeaa)DE-He213 DNA damage (dpeaa)DE-He213
topic	ddc 610 bkl 44.68 misc Whole brain irradiation misc Neurovascular coupling misc Functional hyperemia misc Dementia misc Gait dysfunction misc Neurovascular unit misc Cellular senescence misc DNA damage
topic_unstemmed	ddc 610 bkl 44.68 misc Whole brain irradiation misc Neurovascular coupling misc Functional hyperemia misc Dementia misc Gait dysfunction misc Neurovascular unit misc Cellular senescence misc DNA damage
topic_browse	ddc 610 bkl 44.68 misc Whole brain irradiation misc Neurovascular coupling misc Functional hyperemia misc Dementia misc Gait dysfunction misc Neurovascular unit misc Cellular senescence misc DNA damage
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title	Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence
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title_full	Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence
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author_browse	Ungvari, Zoltan Tarantini, Stefano Hertelendy, Peter Valcarcel-Ares, M. Noa Fülöp, Gabor A. Logan, Sreemathi Kiss, Tamas Farkas, Eszter Csiszar, Anna Yabluchanskiy, Andriy
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title_sort	cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence
title_auth	Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence
abstract	Abstract 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 (CBF) via neuronal activity-dependent 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.
abstractGer	Abstract 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 (CBF) via neuronal activity-dependent 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.
abstract_unstemmed	Abstract 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 (CBF) via neuronal activity-dependent 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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title_short	Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence
url	https://dx.doi.org/10.1007/s11357-017-9964-z
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author2	Tarantini, Stefano Hertelendy, Peter Valcarcel-Ares, M. Noa Fülöp, Gabor A. Logan, Sreemathi Kiss, Tamas Farkas, Eszter Csiszar, Anna Yabluchanskiy, Andriy
author2Str	Tarantini, Stefano Hertelendy, Peter Valcarcel-Ares, M. Noa Fülöp, Gabor A. Logan, Sreemathi Kiss, Tamas Farkas, Eszter Csiszar, Anna Yabluchanskiy, Andriy
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Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence

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