Abstract W P385: Hypertension-Induced Hypoxia Leads to Neurodegeneration in a Novel Model of Accelerated Cerebrovascular Disease
Hypertension is a major risk factor contributing to cerebrovascular diseases such as stroke and vascular cognitive impairment (VCI). Elevated blood pressure leads to cerebral small vessel disease, resulting neuronal cell death and cognitive dysfunction. We developed a unique animal model of clinical VCI in the spontaneously hypertensive stroke prone (SHR-SP) rat, characterized by significant white matter disease, neuroinflammation and behavioral deficits induced by a Japanese Permissive Diet (JPD) and unilateral carotid artery occlusion (UCAO). We hypothesized that the SHR-SP rat has neuropathological changes in the cortex and hippocampus due to effects of hypertension on neurodegeneration. To test the hypothesis, we performed permanent right side UCAO (hypoxia) at 12 weeks (12W) of age in male SHR-SP rats (n=5). Following surgery, rats were placed on a JPD and received 1% NaCl in drinking water (hypertension). Control rats were fed a normal diet and underwent right carotid artery isolation (n=4). A preliminary time course of NeuN and Cresyl Violet staining, from hypoxia onset (12W) to sacrifice (16W), showed decreased neuronal survival and elevated neuroinflammatory response (astro- and micro-gliosis by GFAP and Iba1 staining, respectively) in the experimental group as compared to controls. Microbleeds and endothelial cell damage were observed by Hematoxylin and Eosin histology. Immunohistochemistry showed an up-regulation of hypoxia inducible factor-1α (HIF-1α), implicating a hypoxia-mediated mechanism in neurodegeneration. We observed disruption of the blood brain barrier beginning at 13W, with progressive changes by 16W. MRI-T2 imaging showed significantly larger infarct sizes on the left as compared to the right side hippocampus of experimental rats versus controls (1409656.67±262032 and 1174952.89±145886 (mean±SE), respectively; p<0.009). Our results indicate that chronic hypertension may effect neurodegenerative changes, not only in the white matter, but also in the cortex and hippocampus. Supported by NIH/NINDS RO1 NS045847-07A1.
Author Disclosures: L. Raz: None. K. Bhaskar: None. G.A. Rosenberg: None.
- © 2015 by American Heart Association, Inc.