Cerebral Microvessel Responses to Focal Ischemia

Abstract

Summary:Cerebral microvessels have a unique ultrastructure form, which allows for the close relationship of the endothelium and blood elements to the neurons they serve, via intervening astrocytes. To focal ischemia, the cerebral microvasculature rapidly displays multiple dynamic responses. Immediate events include breakdown of the primary endothelial cell permeability barrier, with transudation of plasma, expression of endothelial cell-leukocyte adhesion receptors, loss of endothelial cell and astrocyte integrin receptors, loss of their matrix ligands, expression of members of several matrix-degrading protease families, and the appearance of receptors associated with angiogenesis and neovascularization. These events occur pari passu with neuron injury. Alterations in the microvessel matrix after the onset of ischemia also suggest links to changes in nonvascular cell viability. Microvascular obstruction within the ischemic territory occurs after occlusion and reperfusion of the feeding arteries ("focal no-reflow" phenomenon). This can result from extrinsic compression and intravascular events, including leukocyte(-platelet) adhesion, platelet-fibrin interactions, and activation of coagulation. All of these events occur in microvessels heterogeneously distributed within the ischemic core. The panorama of acute microvessel responses to focal cerebral ischemia provide opportunities to understand interrelationships between neurons and their microvascular supply and changes that underlie a number of central nervous system neurodegenerative disorders.

Early Release of HMGB-1 from Neurons after the Onset of Brain Ischemia

“…The significance of the inflammatory response to brain ischemia is complex, but there is evidence that in the early phase after ischemia, inflammation contributes to tissue injury, whereas in later stages, inflammation might participate in brain repair Garau et al, 2005;Hara et al, 1997;Kumai et al, 2004;Lovering and Zhang, 2005;Marchetti and Abbracchio, 2005;Wang et al, 1997). In this early phase, in vivo and in vitro evidence is consistent with the paradigm that the endothelium promotes inflammation and recruits circulating leukocytes through the upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, E-selectin, and P-selectin (del Zoppo and Mabuchi, 2003). These recruited leukocytes then release metalloproteinases, which participate in the breakdown of the neurovascular matrix with consequent blood-brain barrier disruption, edema, and/or hemorrhage (Justicia et al, 2003;Kolev et al, 2003;Maier et al, 2004;Ponnampalam and Mayberg, 2004;Veldhuis et al, 2003;Wang and Lo, 2003).…”

Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study

“…Hypoperfusion, through various mechanisms, has been proposed as a probable candidate for structural and functional brain changes,34, 43, 44 most likely through reduced cardiac output for systolic dysfunction. Further research is required to clarify the causative role of diastolic dysfunction; however, it has recently been associated with the development and progression of white matter lesions, relating to heightened risks of cognitive decline.…”

Cerebral Blood Volume Affects Blood–Brain Barrier Integrity in an Acute Transient Stroke Model

“…Physiologically, the failure of complete restoration of the CBV can result from the 'no-reflow' phenomenon, that is, lingering obstruction of the downstream microvasculature, even after the main feeding artery is reopened. 21 This condition is initially induced by intravascular coagulation and endothelial swelling. 21 Subsequently, progressive lactic acidosis due to insufficient reflow exacerbates edema in the neurovascular unit, thereby aggravating vascular occlusion and interfering with the restoration of blood perfusion.…”