Effects of scopolamine challenge on regional cerebral blood volume. A pharmacological model to validate the use of contrast enhanced magnetic resonance imaging to assess cerebral blood volume in a canine model of aging.
Cognitive impairment resulting from disruption of cholinergic function may occur through modulation of cerebrovascular volume (CBV). In the present study, dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) was used to examine cerebrovascular volume in young and old dogs during baseline and after administration of a cholinergic antagonist (scopolamine). In the first study, 24 animals (2-15 years of age) were given a baseline scan followed by a second scan after scopolamine administration (30 microg/kg). Gray matter rCBV was significantly higher than white matter rCBV during baseline and scopolamine administration. In the second study a subset of 7 dogs (4 young and 3 old) received scopolamine before anesthesia was induced for a second DSC-MRI scan. Consistent with the first study, gray matter rCBV was significantly higher than white matter rCBV. Scopolamine administered before anesthesia however, resulted in higher rCBV values compared to baseline in cerebral gray matter. Additionally, rCBVs were higher in young dogs at baseline in gray and white matter and marginally higher in gray matter when scopolamine was administered before anesthesia. These results indicate that in the dog, rCBV varies with brain compartment, decreases with age, and that DSC-MRI provides a measure of cerebrovascular function which may be related to age-dependent changes in cognition, brain structure, and neuropathology.
Tapp
P Dwight
PD
John Tu and Thomas Yuen Center for Functional Onco-imaging, University of California, 164 Irvine Hall, Irvine, CA, USA.
Chu
Yong
Y
Araujo
Joseph A
JA
Chiou
Jr-Yuan
JY
Head
Elizabeth
E
Milgram
Norton W
NW
Su
Min-Ying
MY
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D007089:Image Enhancement / Q000379:methods; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D012601:Scopolamine; D018709:Statistics, Nonparametric
D012601:Scopolamine