Hemodynamic effects of combined focal cerebral ischemia and amyloid protein toxicity in a rat model: a functional CT study

• Published in: PloS one Vol. 9; no. 6; p. e100575
• Main Authors: Yang, Jun, d'Esterre, Christopher D, Amtul, Zareen, Cechetto, David F, Lee, Ting Yim
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27-06-2014; Public Library of Science (PLoS)
• Subjects: Administration, Intravenous; Alzheimer's disease; Amyloidogenic Proteins - toxicity; Animal cognition; Animals; Biology and Life Sciences; Biophysics; Blood; Blood flow; Blood volume; Blood Volume - drug effects; Brain; Brain - blood supply; Brain - diagnostic imaging; Brain - drug effects; Brain - physiopathology; Brain Ischemia - diagnostic imaging; Brain Ischemia - physiopathology; Brain Mapping; Brain research; Cerebral blood flow; Cognitive ability; Computed tomography; Contrast Media - administration & dosage; Dementia; Disease Models, Animal; Hemodynamics; Hemodynamics - drug effects; Histopathology; Hypervolemia; Image acquisition; Image contrast; Ischemia; Laboratories; Male; Medical imaging; Medicine and Health Sciences; Microvasculature; Microvessels - diagnostic imaging; Microvessels - drug effects; Microvessels - pathology; Neostriatum; Neurodegenerative diseases; Neuroimaging; Neurosciences; NMR; Nuclear magnetic resonance; Peptides; Perfusion; Proteins; Rats; Rats, Wistar; Research and Analysis Methods; Rodents; Stroke; Surgery; Tomography, X-Ray Computed; Toxicity; Transgenic animals; β-Amyloid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0100575

Clinical evidence indicates that cerebral ischemia (CI) and a pathological factor of Alzheimer's disease, the β-amyloid (Aβ) protein, can increase the rate of cognitive impairment in the ageing population. Using the CT Perfusion (CTP) functional imaging, we sought to investigate the interaction between CI and the Aβ protein on cerebral hemodynamics.
A previously established rat model of CI and Aβ was used for the CTP study. Iodinated contrast was given intravenously, while serial CT images of sixteen axial slices were acquired. Cerebral blood flow (CBF) and blood volume (CBV) parametric maps were co-registered to a rat brain atlas and regions of interest were drawn on the maps. Microvascular alteration was investigated with histopathology.
CTP results revealed that ipsilateral striatum of Aβ+CI and CI groups showed significantly lower CBF and CBV than control at the acute phase. Striatal CBF and CBV increased significantly at week 1 in the CI and Aβ+CI groups, but not in the Aβ alone or control group. Histopathology showed that average density of dilated microvessels in the ipsilateral striatum in CI and Aβ+CI groups was significantly higher than control at week 1, indicating this could be associated with hyperperfusion and hypervolemia observed from CTP results.
These results demonstrate that CTP can quantitatively measure the hemodynamic disturbance on CBF and CBV functional maps in a rat model of CI interacting with Aβ.