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Neurovascular uncoupling predicts cognitive decline and gait abnormalities in a clinically relevant mouse model of whole brain irradiation
Author(s) -
Yabluchanskiy Andriy,
Tarantini Stefano,
Hertelendy Peter,
ValcarcelAres Marta Noa,
Gautam Tripti,
Farkas Eszter,
Sonntag William E.,
Csiszar Anna,
Ungvari Zoltan
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.681.4
Subject(s) - neurovascular bundle , cognitive decline , medicine , cerebral blood flow , gait , cardiology , cognition , physical medicine and rehabilitation , psychology , neuroscience , anesthesia , pathology , dementia , disease
Whole brain irradiation (WBI) is known to promote accelerated brain senescence and leads to progressive cognitive dysfunction in up to 50% of tumor patients surviving long‐term after treatment, due to, at least in part, gamma‐irradiation induced cerebromicrovascular injury. Moment‐to‐moment adjustment of cerebral blood flow (CBF) via neurovascular coupling (NVC) has a critical role in maintenance of healthy cognitive function. To determine whether cognitive decline induced by WBI associate with impaired NVC, C56BL/6 mice (3 mo) 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 NVC (laser Doppler flowmetry) at 3 and 6 months post‐irradiation. We found that mice with WBI exhibited impaired NVC at 3 months post‐irradiation, which was associated with impaired performance in the radial arm water maze, while gait parameters remained unaltered. At 6 months post‐irradiation persisting neurovascular dysfunction and cognitive impairment were evident, which were associated with significant impairment in gait coordination (including changes in the regularity index and phase dispersion). Collectively, our findings provide evidence for early and persisting neurovascular un‐coupling after a clinically relevant protocol of fractionated WBI, which predict early manifestations of cognitive impairment. Support or Funding Information This work was supported by grants from the American Heart Association, the National Center for Complementary and Alternative Medicine, and the National Institute on Aging