The important role of atherosclerosis in pathophysiology of Alzheimer's Disease has become evident.Mechanisms such as hyperlipidemia,inflammation,abdominal obesity and insulin resistance are important yet they may...The important role of atherosclerosis in pathophysiology of Alzheimer's Disease has become evident.Mechanisms such as hyperlipidemia,inflammation,abdominal obesity and insulin resistance are important yet they may not fully explain the specific involvement of the Circle of Willis in these pathologies.The Circle of Wills is a complex geometrical structure which has several areas with different curvature as well as various branching angles of vessels composing the circle.The hemodynamics in this region should take into account the Dean number which indicates the influence of curvature on the resistance to blood flow.Thus,areas with various curvature and angles may have different hemodynamics and there are certain areas in the Circle of Willis that are more likely to develop atherosclerotic changes.Therefore,this could suggest the novel pathophysiological pathway resulting from the geometric peculiarities of the Circle of Willis.One of the directions of future research is to examine whether specific areas of the Circle of Willis are more likely to develop atherosclerotic changes compared to other ones.Selective areas of the Circle of Willis affected by atherosclerotic changes could indicate the primary role of atherosclerosis promoting Alzheimer's disease although other pathophysiological mechanisms suggesting the opposite direction should be also examined in prospective studies.展开更多
Despite the impressive efficacies demonstrated in preclinical research,hundreds of potentially neuroprotective drugs have failed to provide effective neuroprotec-tion for ischemic stroke in human clinical trials.Lack ...Despite the impressive efficacies demonstrated in preclinical research,hundreds of potentially neuroprotective drugs have failed to provide effective neuroprotec-tion for ischemic stroke in human clinical trials.Lack of a powerful animal model for human ischemic stroke could be a major reason for the failure to develop successful neuroprotective drugs for ischemic stroke.This review recapitulates the available cerebral ischemia animal models,provides an anatomical comparison of the circle of Willis of each species,and describes the functional assessment tests used in these ischemic stroke models.The distinct differences between human ischemic stroke and experimental stroke in available animal models is explored.Innovative animal models more closely resembling human strokes,better techniques in functional out-come assessment and better experimental designs generating clearer and stronger evidence may help realise the development of truly neuroprotective drugs that will benefit human ischemic stroke patients.This may involve use of newer molecules or revisiting earlier studies with new experimental designs.Translation of any resultant successes may then be tested in human clinical trials with greater confidence and optimism.展开更多
文摘The important role of atherosclerosis in pathophysiology of Alzheimer's Disease has become evident.Mechanisms such as hyperlipidemia,inflammation,abdominal obesity and insulin resistance are important yet they may not fully explain the specific involvement of the Circle of Willis in these pathologies.The Circle of Wills is a complex geometrical structure which has several areas with different curvature as well as various branching angles of vessels composing the circle.The hemodynamics in this region should take into account the Dean number which indicates the influence of curvature on the resistance to blood flow.Thus,areas with various curvature and angles may have different hemodynamics and there are certain areas in the Circle of Willis that are more likely to develop atherosclerotic changes.Therefore,this could suggest the novel pathophysiological pathway resulting from the geometric peculiarities of the Circle of Willis.One of the directions of future research is to examine whether specific areas of the Circle of Willis are more likely to develop atherosclerotic changes compared to other ones.Selective areas of the Circle of Willis affected by atherosclerotic changes could indicate the primary role of atherosclerosis promoting Alzheimer's disease although other pathophysiological mechanisms suggesting the opposite direction should be also examined in prospective studies.
基金Science and Engineering Research Board,Grant/Award Number:CRG/2019/002076Council of Scientific and Industrial Research,Grant/Award Number:09/805(0012)/2019-EMR-I。
文摘Despite the impressive efficacies demonstrated in preclinical research,hundreds of potentially neuroprotective drugs have failed to provide effective neuroprotec-tion for ischemic stroke in human clinical trials.Lack of a powerful animal model for human ischemic stroke could be a major reason for the failure to develop successful neuroprotective drugs for ischemic stroke.This review recapitulates the available cerebral ischemia animal models,provides an anatomical comparison of the circle of Willis of each species,and describes the functional assessment tests used in these ischemic stroke models.The distinct differences between human ischemic stroke and experimental stroke in available animal models is explored.Innovative animal models more closely resembling human strokes,better techniques in functional out-come assessment and better experimental designs generating clearer and stronger evidence may help realise the development of truly neuroprotective drugs that will benefit human ischemic stroke patients.This may involve use of newer molecules or revisiting earlier studies with new experimental designs.Translation of any resultant successes may then be tested in human clinical trials with greater confidence and optimism.
