Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

Abstract

The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury following ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier (BBB) is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in BBB integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events.

Changes in the Vascular Extracellular Matrix as a Potential Cause of Myocyte Loss via Anoikis in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

“…Our study on arterial vessels derived from patients with CADASIL diagnosis revealed changes in compounds of vascular ECM (increased immune expression of collagen IV and fibronectin, and decreased immune expression of laminin), as well as increased immune reactivity to metalloproteinases MMP-2 and MMP-9 [5]. In vessels exchange of ECM compounds is very dynamic and reflects their functional state.…”

Impact of Metabolic Diseases on Cerebral Circulation: Structural and Functional Consequences

“…Given that 1) constant CBF and BBB integrity are essential for brain homeostasis, and 2) cerebral circulation is an early target in these conditions, it is highly likely that changes in cerebrovascular structure and physiology play an important role in the onset and progression of these diseases. We would like to direct readers to two excellent articles that review the impact of cerebrovascular disease on ischemic stroke and cognitive impairment (60, 122) as well as to a scientific statement from the American Health Association that presents evidence on vascular contributions to cognitive impairment and dementia (103). This important statement identified the need for two lines of research: imaging of neurovascular changes over the disease course and studies on intensive reduction of vascular risk factors in high-risk groups.…”

Neurovascular Oxidative Stress and Autonomic Modulation Contributing to QT Interval Variations in Acute Large Artery Ischemic Stroke

“…The cortical network and insular lobe function of subcortical area injury during large artery ischemic stroke have been reported [11]. Ischemic insults produce an excess amount of free radicals, especially in the reperfused ischemic area [35]. Oxidative stress causes neuronal necrosis and death.…”

“…Recently, it has been reported that NO plays a vital role at medullary neuron with H 2 O 2 as neuromodulator of redox signal from ROS formation and they are related with sympathetic activity drive at medulla for central hypertension [37]. Recently, NO and H 2 O 2 are coupled relaxing factors in brain corresponding with increasing cerebral blood flow during cerebrovascular reactivity in normal and lacunar stroke (small artery stroke) [19,[32][33][34][35][36][37][38]. Both of them are gases that diffuse rapidly to cerebrospinal fluid and then in blood circulation within 30 seconds as assessed by cerebrovascular reactivity [38].…”