The effects of hypertension on cerebral atherosclerosis in the cynomolgus monkey (original) (raw)
Related papers
Microinfarction as a result of hypertension in a primate model of cerebrovascular disease
Acta Neuropathologica, 1999
Ten adult cynomolgus monkeys were studied as a non-human primate model of hypertensive cerebrovascular disease. Seven were made hypertensive by surgical coarctation of the aorta and three served as unoperated controls. After survival periods of 8-30 months, the brains were serially sectioned and surveyed for neuropathological changes. The most conspicuous change was minute areas of microinfarction in the white and gray matter. The lesions were of irregular shape with an average maximum diameter of less than 0.5 mm. They were slightly larger in the gray than in the white matter and appeared to be of different ages. Their area of predilection was the white matter of the forebrain, with smaller numbers in the cerebral cortex and scattered lesions elsewhere in the forebrain, brain stem and cerebellum. These microinfarcts did not correspond to usually described lesions in the human brain in hypertension or in other animal models of hypertensive cerebrovascular disease. We suggest that they represent an early change in the natural history of hypertensive neuropathology.
Occurrence of stroke in a nonhuman primate model of cerebrovascular disease
Stroke, 1988
A relation between hypertension, atherosclerosis, and stroke is well documented in humans. We report a similar relation in two hypertensive cynomolgus monkeys with severe cerebral atherosclerosis. In our primate model hypertension is induced by surgical coarctation of the aorta. These monkeys, when fed an atherogenic diet, develop severe cerebrovascular atherosclerosis. In this setting two monkeys developed spontaneous cerebral hemispheric strokes that occurred during treatment of hypertension. Since the strokes were topographically related to severe atherosclerotic narrowing of cerebral arteries and occurred without evidence of either thrombosis or embolization, they are presumed to be related to disturbances of blood flow. In both humans and animals cerebral perfusion is autoregulated to a constant flow over a wide range of mean arterial blood pressures. In hypertension both the upper and lower limits of autoregulation are increased. With treatment of hypertension readaptation to ...
Research Priorities for Intracranial Atherosclerotic Diseases
Journal of Neuroimaging, 2009
The current review summarizes the characteristics of existing experimental models for intracranial atherosclerosis in rabbits, pigs, and dogs with potential implications for research. New methodologies for understanding plaque morphology, and plaque quantitation and its prognostic implications are important for risk stratification in regards to ischemic events and lesion progression. A potential treatment strategy for intracranial atherosclerotic disease may be aimed at medical therapies that induce plaque regression. The treatment with statins to stabilize and/or promote plaque regression of intracranial atherosclerotic lesions is largely inferred from data in the coronary literature. In patients with multisegmented intracranial atherosclerotic diseases with no other therapeutic option, angiogenic growth factors may represent a new venue.
Veterinary Sciences, 2022
The atherosclerotic lesion is a principal hallmark of atherosclerotic animal models. This study aimed to assess lesions of the carotid artery in Indonesian cynomolgus monkeys exposed to an IPB-1 atherogenic diet. A total of 20 adult male cynomolgus monkeys received the local IPB-1 diet for two years. Blood lipid profiles, morphology, and carotid ultrasound of monkeys were measured. Nine of them were euthanized to confirm atherosclerotic lesions. Common carotid arteries (CCA) and carotid bifurcation (BIF) samples were collected and stained using Verhoef-van Giessen and CD68 immunohistochemistry. The results reveal the presence of severe atherosclerosis plaques in six out of nine animals (66.7%) corresponding to intermediately and hyper-responsive groups. The hyper-responsive group displayed the highest response in the developing intimal area (IA) at the CCA (0.821 mm2), whereas the hyporesponsive group had the smallest IA (0.045 mm2) (p = 0.0001). At the BIF, the hyporesponsive group...
A Primate Model of Hypertensive Cerebrovascular Disease
Central Nervous System Diseases, 2000
Cerebrovascular disease (CVD) in humans has been shown to produce a variety of cognitive impairments ranging from selective deficits to wide-range dementia. Among the risk factors for CVD (e.g., age, diabetes mellitus, serum lipids, obesity, cardiac disease), arterial hypertension has been identified as key (1) affecting more than 25% of the adult population of the United States (2). Gross effects of extreme hypertension are well known and include a four times greater risk for CVD than normotensive individuals (3). For the most part, hypertension is an asymptomatic disorder, but recently it has been the focus of attention on its possible detrimental effects on cognitive function. Indeed, over the past two decades, evidence has accumulated to suggest that hypertension in humans produces, in many cases, a significant impairment in several domains of cognitive function. But because of the inherent limitations of human research, even with recent advances in magnetic resonance and positron emission imaging technology, our understanding of the neurobiological basis for hypertensive related cognitive impairment is unknown. It is also unknown to what extent the changes in cognition that are associated with hypertension represent the first stage in the development of CVD and vascular dementia. Animal studies using rodents, rabbits, and, to a lesser extent, nonhuman primates have contributed significantly to our understanding of the underlying mechanisms and pathological changes associated with hypertension and CVD, but we have yet to address the question of the neural basis for the neuropsychological consequences of hypertension. This chapter describes the development of a primate model of hypertensive CVD incorporating a mUltidisciplinary study that includes the assessment of cognitive function. 2. DEVELOPMENT OF THE MODEL As clearly demonstrated by the contributions contained in this volume, the use of animal models provides a major approach to the study of human disease. The assessment of disease processes is difficult and rather limited with human subjects owing to From: Central Nervous System Diseases
A pathological perspective on the natural history of cerebral atherosclerosis
International journal of stroke : official journal of the International Stroke Society, 2015
The natural history of intracranial large artery atherosclerosis has been mainly described from lumen-based imaging studies, and much of what is reported to be known about atherosclerosis is derived from non-cerebral arteries. To test the hypothesis that atherosclerosis is only partially represented by stenosis and that advanced atherosclerosis is more common that severe stenosis in noncardioembolic infarcts. Cerebral large arteries from 196 autopsy cases were studied. The revised American Heart Association classification for atherosclerosis was used to determine the phenotype in each available artery. Cross-sectional lumen stenosis was obtained as defined by the Glagov's method. As age of cases increased, there was a progressive increment in the frequency of atherosclerotic lesions, rising from 5% of all arteries at age 20-40, to more than 40% at age 60 or older. Stenosis also increased with age: less than 3% of the arteries in those ≤50 years had >40% stenosis, while one ou...
Atherosclerosis and Arterial Blood Pressure in Mice
Current Drug Targets
Increased blood pressure is a consistent risk factor for the development of atherosclerotic diseases in humans, although the basis for this relationship is unknown. Genetically engineered mice are now commonly used to study mechanisms of atherosclerosis. More recently, blood pressure can be reliably measured in conscious mice using either tail cuff or telemetric techniques. Thus, mouse models permit the investigation of the complex interactions of blood pressure and atherogenesis. Most mouse models exhibiting hypertension have increased atherosclerotic lesion size, although there have been exceptions to these findings. Also, there are several reports that have used methods to decrease blood pressure and demonstrated reduced atherosclerosis. In contrast, there are many studies in which atherosclerosis has been altered without changes in blood pressure, and conversely, studies in which blood pressure changes did not alter atherosclerosis. Studies that have specifically defined the role of elevated systolic blood pressure on the development of atherosclerosis have uniformly demonstrated that pressure per se is not responsible for changes in lesion development. Thus, while increased systolic blood pressure is frequently associated with atherosclerosis, the stimulus for the hypertension appears to be the major determinant of atherogenesis rather than pressure per se. A consistent theme in the literature has been that perturbations of the renin angiotensin system display the strongest correlations between blood pressure and atherosclerosis.
The effects of hypertension on the cerebral circulation
American Journal of Physiology-Heart and Circulatory Physiology, 2013
Maintenance of brain function depends on a constant blood supply. Deficits in cerebral blood flow are linked to cognitive decline, and they have detrimental effects on the outcome of ischemia. Hypertension causes alterations in cerebral artery structure and function that can impair blood flow, particularly during an ischemic insult or during periods of low arterial pressure. This review will focus on the historical discoveries, novel developments, and knowledge gaps in 1) hypertensive cerebral artery remodeling, 2) vascular function with emphasis on myogenic reactivity and endothelium-dependent dilation, and 3) blood-brain barrier function. Hypertensive artery remodeling results in reduction in the lumen diameter and an increase in the wall-to-lumen ratio in most cerebral arteries; this is linked to reduced blood flow postischemia and increased ischemic damage. Many factors that are increased in hypertension stimulate remodeling; these include the renin-angiotensin-aldosterone syste...