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001-es BibID:BIBFORM085446
035-os BibID:(WOS)000401331200004 (Scopus)85017238534
Első szerző:Ungvári Zoltán
Cím:Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence / Ungvari Zoltan, Tarantini Stefano, Hertelendy Peter, Valcarcel-Ares M. Noa, Fülöp Gabor A., Logan Sreemathi, Kiss Tamas, Farkas Eszter, Csiszar Anna, Yabluchanskiy Andriy
Dátum:2017
ISSN:2509-2715 2509-2723
Megjegyzések: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 ?-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.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Whole brain irradiation
Neurovascular coupling
Functional hyperemia
Dementia
Gait dysfunction
Neurovascular unit
Cellular senescence
DNA damage
Megjelenés:GeroScience. - 39 : 1 (2017), p. 33-42. -
További szerzők:Tarantini, Stefano Hertelendy Péter Valcarcel Ares, Marta Noa Fülöp Gábor Áron (1988-) (általános orvos) Logan, Sreemathi Kiss Tamás Farkas Eszter Csiszár Anna Yabluchanskiy, Andriy
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