Cerebrovascular and brain metabolism reviews最新文献

This review focuses on the natural history of symptomatic and asymptomatic carotid stenosis and on the risk/benefit ratio of carotid endarterectomy. Five randomized trials for symptomatic stenosis and four trials for asymptomatic carotid occlusive disease are reviewed. Carotid endarterectomy has been proved effective in reducing stroke risk in symptomatic 70-99% stenosis. Conclusive results are still pending for moderate symptomatic stenosis and the asymptomatic lesion. Surgical controversies and techniques are discussed. Algorithms for management of symptomatic and asymptomatic stenosis are offered.

The cerebrovascular and metabolic changes associated with traumatic injury to the CNS may be associated, in part, with pathologic alterations in endogenous neurochemical systems, including those involved with normal neurotransmission. These events may include alterations in neurotransmitter synthesis, release, or re-uptake mechanisms or changes in pre- or postsynaptic receptor activity. Other changes may include alterations in synthesis and release of endogenous neuroprotective compounds (e.g., antioxidants), the pathologic expression and release of endogenous "autodestructive" compounds, or regional changes in specific neurochemical factors known to be associated with inflammation (e.g., cytokines), or neuronal growth and regeneration (e.g., growth factors). Although the timing of the precise cascade of neurochemical events following CNS injury is poorly understood, recent identification of specific neurochemical alterations following traumatic brain injury provides an opportunity for the development and employment of therapeutic agents designed to modify gene expression, synthesis, release, receptor, or functional activity of these factors with subsequent attenuation of local secondary tissue damage. This article is a compendium of recent studies suggesting that modification of posttraumatic events with pharmacologic strategies can improve outcome and promote functional recovery in both animal models of traumatic CNS injury and in selected clinical trials.

Although the microvascular compartment contributes significantly to intravascular volume, its importance to disease is often underestimated. Events surrounding cerebral ischemia and recent interest in strategies which may lead to cerebral artery reperfusion in thrombotic or embolic stroke have raised enquiries about the role(s) the microvasculature may play during ischemia and reperfusion. Except in a few instances, little is known about the organization of the microvasculature in cerebral tissue. However, it is apparent that ischemia, inflammatory insults, and infectious processes affect the cerebral microvascular endothelia, cellular elements of the circulating blood compartment, and hemostasis. The precise mechanisms are under study. Observations in isolated microvascular systems from brain tissue, direct visualization of the pial cortical vasculature, and in situ preparations which allow study of the subcortical microvasculature have added to our understanding of these processes. During focal cerebral ischemia and reperfusion alterations of endothelial cell reactivity, coagulation system activation, and granulocyte-endothelial cell interactions are a few of the events affecting microvascular integrity which have been documented. Oxygen free radical generation, selectin and integrin expression and intercellular adhesion, vasomotor responses, endothelial permeability changes, and coagulation system and platelet activation are some of the microvascular processes currently under study which appear to be triggered during ischemia and reperfusion. In view of these events the responses of the cerebral microvasculature to ischemic injury remain relatively unexplored.

The cytokine tumor necrosis factor (TNF-alpha) is a pleotrophic polypeptide that plays a significant role in brain immune and inflammatory activities. TNF-alpha is produced in the brain in response to various pathological processes such as infectious agents [e.g., human immunodeficiency virus (HIV) and malaria], ischemia, and trauma. TNF-alpha mRNA is rapidly produced in response to brain ischemia within 1 h, reaches a peak at 6-12 h post ischemia, and subsides 1-2 days later. TNF-alpha mRNA expression corresponds in a temporal fashion to other cytokines such as interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (KC), and IL-1 and precedes the infiltration of inflammatory cells into the injured zone. TNF-alpha is present early in neuronal cells in and around the ischemic tissue (penumbra), yet at later time points, the peptide is found in macrophages in the infarcted tissue. TNF-alpha has been demonstrated to cause expression of proadhesive molecules on the endothelium, which results in leukocyte accumulation, adherence, and migration from capillaries into the brain. Furthermore, TNF-alpha activates glial cells, thereby regulating tissue remodeling, gliosis, and scar formation. Thus, evidence is emerging in support of a role for TNF-alpha in injury induced by infectious, immune, toxic, traumatic, and ischemic stimuli. TNF-alpha promotes inflammation by stimulation of capillary endothelial cell proinflammatory responses and thereby provides leukocyte adhesion and infiltration into the ischemic brain. The evidence generated so far suggests that agents that suppress TNF-alpha's production or actions will reduce leukocyte infiltration into ischemic brain regions and thereby diminish the extent of tissue loss.

Single photon emission computed tomography (SPECT) is a technique for producing regional maps of the in vivo distribution of radioactively labelled tracers without either the complexity or the cost of positron emission tomography (PET). Use of commercially available single photon emitting tracers such as 99mTc, 123I, or 201Th with longer half-lives than positron emitters eliminates the need for an on-site cyclotron and greatly simplifies the radiopharmacy requirements. In addition, the ability to produce images using gamma cameras which are routinely available in most nuclear medicine departments has considerably reduced the capital asset cost of imaging. SPECT is not an inexpensive procedure but it is much cheaper than PET. It is not possible to use the ideal biological labels of carbon, nitrogen, or oxygen with SPECT or to measure metabolic rates for oxygen or glucose. It is, however, now possible to image the distribution of cerebral blood flow with a reasonably well-validated technique, to investigate tumour viability, and to study an ever-increasing range of neurotransmitter receptor systems using SPECT. SPECT may have its technical limitations but it is the functional imaging technique which is likely to be available to most clinicians and, as experience with its application to a variety of pathological conditions grows, a much broader benefit from functional neuroimaging than could be produced by PET alone will result. The purpose of this review is not to compare SPECT with PET, but to give an overview of how SPECT works and what has been established in studies of various pathologies. In some cases, the clinical role of SPECT has already been established and in some it is emerging, but in other cases SPECT is a measurement tool for research purposes which is unlikely ever to be used routinely.

This chapter reviews the evidence that challenges traditional and unproven notions which perpetuate the singular importance of constriction and dilation to the genesis of migraine pain. New data in experimental laboratory models suggest that migraine headache may develop primarily from metabolic/neurophysiological events (as yet unidentified) within the cortical mantle, or from a disturbance in those regions of brain which closely approximate the distribution of trigeminovascular fibers innervating meningeal blood vessels. Accordingly, this chapter will review the consequences of trigeminovascular activation to pain and meningeal inflammation, and will summarize emerging molecular and pharmacological data suggesting that ergot alkaloids and sumatriptan alleviate pain primarily via activation of pre-junctional 5-HT1 heteroreceptors residing on primary afferent trigeminovascular fibers.

Functional neuroimaging techniques such as positron and single-photon emission computed tomography (PET and SPECT) have contributed to our knowledge of pathophysiological changes in ischemic stroke. Determinations of cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2) permit the discrimination of various compensatory mechanisms in occlusive vascular disease, where changes in the CBF/CBV ratio indicate a perfusional reserve and increases in the oxygen extraction fraction (OEF), a metabolic reserve, that prevent ischemic tissue damage during graded flow decreases. Early in the course of acute ischemia, CBF and CMRO2 below a certain threshold (approximately 12 ml/100 g/min and/or 65 mumol/100 g/min, respectively) indicate irreversible tissue damage, while preservation of CMRO2 with decreased flow resulting in increased OEF ("misery perfusion") suggests still viable tissue up to 48 h after the attack, which, however, turns into necrosis in most instances during the following period. In a few instances such tissues can survive, suggesting a potential for effective therapy. Transient ischemic attacks are caused by less severe regional flow disturbances and the consequent metabolic changes are not so significant. In these cases the impact of obstructive vascular changes on hemodynamic reserve can be evaluated by functional tests applying CO2 or acetazolamide. While the regional cerebral metabolic rate of glucose (rCMRglu) in early ischemia is often not coupled to flow or CMRO2 and might even be increased (nonoxidative glycolysis with consequent tissue lactacidosis), this variable is the best indicator of permanent impairment of tissue function. (ABSTRACT TRUNCATED AT 250 WORDS)

About 4% of adults have asymptomatic neck bruits, and this frequency increases with age. Only a small number of these (about 25%), however, have asymptomatic carotid stenosis (ACS), and only 10% of these have stenoses > 75%. The vascular outcome for patients with ACS depends upon the severity of carotid stenosis, all outcomes worsening after 75-80% stenoses. For stenoses < 50%, annual stroke rate is about 1% and does not change in stenoses 50-75%, but over 75%, annual stroke rate increases to 3.3% per year. Ischaemic cardiac event rate is 2.7% annually for stenoses < 50%, 6.6% for those 50-75%, and 8.3% for stenoses > 75%. Annual vascular death rates also rise from 1.8%, 3.3% and 6.5% respectively. Stroke risk factors such as hypertension and smoking are important in early plaque formation, but when plaques become stenosing, local hemodynamic factors such as turbulence are the major factors in arterial remodelling. No medical or surgical therapy has yet been found effective, but current surgical randomized trials may reveal the answer in the near future.

A great deal of knowledge has been accumulated in recent years, concerning the aging human brain in health and disease, with the advent of newer methods of measuring cerebral blood flow (CBF) and metabolism. It is well documented that even in normal aging, the functional metabolism of the brain and its blood supply inevitably decline. This accounts for the widespread clinical observations that the young tolerate disorders of the brain better than do the elderly. It also accounts for difficulties in correctly diagnosing and treating cognitive disorders among the elderly. Neuronal and vascular reserves become progressively depleted during normal aging, so that one or more different disease processes may contribute to cognitive declines. Computed tomography (CT) densitometry, coupled with xenon-enhanced CT CBF measurements, provide a noninvasive method for separating the changes within cerebral cortex, subcortex, and white matter that occur in normal aging from those due to pathological abnormalities.

Alzheimer disease (AD) is an exceedingly complex disorder in which numerous populations of neurons and neurotransmitter systems are damaged or destroyed. Effective treatment of the cognitive symptoms of AD does not exist, and new targets for therapeutic intervention are needed desperately. Traditionally, the neurotransmitter receptors have been the focus of new neuropsychopharmacological agents, so it seems reasonable to assess the status of these receptors in the AD brain. In this article, we review the quarter century of receptor research in AD. The limitations of receptor studies, in general, and the particular limitations of studying AD tissue are discussed. The cholinergic and glutamatergic systems have been implicated most directly in normal cognitive function, so the receptors for these neurotransmitters are emphasized in this review. We have attempted to point out the possible neurobiological roles and potential clinical significance of the various receptors in AD. Investigation of neurotransmitter receptors in AD provides a rational approach to the development of therapeutic and diagnostic strategies, and, at a minimum, should lead to a better understanding of the neurobiology of AD.