Clinical neuroscience (New York, N.Y.)最新文献

The mechanisms of reperfusion damage following focal cerebral ischemia are not known in detail. Recent results, however, strongly suggest that reactive oxygen species (ROS), generated during the reperfusion period, may trigger the reperfusion injury. Mitochondrial calcium overload and a permeability transition (PT) of the inner mitochondrial membrane have been shown to play an important role in production of ROS by the mitochondria. The immunosuppressant cyclosporin A (CsA), which inhibits mitochondrial PT, protects against delayed neuronal necrosis of the hippocampal CA1 sector following transient forebrain/global ischemia. In focal ischemia ("stroke"), expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) may lead to production of ROS by polymorphonuclear (PMN) leukocytes, which suggests the involvement of inflammatory and immunological reactions in reperfusion damage. The spin trap alpha-phenyl-N-tert-butyl nitrone (PBN) reduces infarct size and prevents a secondary mitochondrial dysfunction due to reperfusion, probably scavenging free radicals at the blood-endothelial cell interface.

It is now generally accepted that diabetes can alter central nervous system (CNS) function. Even in the absence of overt cerebrovascular accidents or repeated hypoglycemic reactions, uncontrolled hyperglycemia is associated with cognitive changes. These changes are documented both in patients with diabetes as well as in animal models of experimental diabetes. The cognitive impairment can be ameliorated with optimization of blood glucose control. The potential causes of CNS dysfunction in diabetes can be broadly categorized as either vascular causes including changes in the blood-brain barrier and metabolic changes. The latter causes include repeated hypoglycemic episodes, hyperglycemia, hyperosmolality, acidosis, ketosis, neuroendocrine or neurochemical changes. The other contributory causes of CNS dysfunction in diabetes include the presence of hypertension, uremia, peripheral and autonomic neuropathy and multiple drug use.

Autoimmunity has been implicated in the pathogenesis of diabetic neuropathy. A number of putative target antigens have been investigated in the attempt to find a relationship between the presence of autoantibodies and the presence of neuropathy. Attention has been given to antibodies against nerve growth factor, adrenal medulla, sympathetic and parasympathetic structures, glutamic acid decarboxylase and phospholipids. Data in the literature do not support a clear-cut difference in frequency of positivity or titres between patients with or without diabetic neuropathy. Moreover, it is not clear whether autoantibodies to the above-mentioned antigens, whenever present, play a role in causing nerve damage or if they simply reflect the presence of nerve damage. Longitudinal studies are needed to clarify some conflicting data in the literature.

The rod and cone systems of the mammalian retina differ in their structure and functional properties as well as in their metabolic characteristics. This article summarizes basic observations on retinal glucose metabolism reflected in retinal electrophysiology. Metabolic factors might be related to the complex pathogenesis of diabetic retinopathy. Effects of changing glucose concentration and, independently, of insulin on retinal responses obtained in an isolated mammalian eye preparation in vitro and also in vivo are presented. Electron microscopy (EM)-histochemical data reveal a distinctive distribution of glycogen in glia and in various subclasses of neurons in the cat retina. Low glucose, corresponding to hypoglycemia in vivo, affected the light-evoked electrical responses from the rod system, but not from the cone system in vitro. This could be confirmed in the anesthetized cat under glucose clamp conditions. Insulin had no influence on physiological retinal function, except under conditions of low glucose, where it enhanced the reduction in b-wave amplitude. This effect is interpreted as a sign of increased glucose utilization by the retinal Müller (glial) cells.

Stroke is a major cause of disability and death each year in the United States. Most cases result from atherosclerotic disease at the carotid bifurcations. The risk of such events can be reduced by carotid endarterectomy in both symptomatic and asymptomatic patients with severe occlusive disease documented by imaging studies. A noninvasive means of determining the degree of stenosis is desirable due to morbidity, mortality, and cost associated with catheter angiography. At the present time the main role of MRA is as a screening test to determine who should undergo catheter angiography.

Magnetic resonance angiography (MRA) and venography (MRV) are useful tools in the diagnosis and analysis of both intracranial and head and neck tumors. These procedures illuminate the three-dimensional relationships of the tumors and the adjacent cerebral vasculature. Contrast administration allows further analysis of these lesions. Research continues to improve the spatial resolution that may preclude conventional angiography. For the first time, MRA allows non-invasive diagnosis of neurovascular conditions such as trigeminal neuralgia and pulsatile tinnitus. This accurate diagnosis revolutionizes therapy. Although MRA has certain limitations, its role continues to expand. The value of MRA for diagnosis and treatment planning is paramount.

Anterior ischemic optic neuropathy (AION) is an entity which involves infarction of the optic disc head. Factors involved with the arteritic variety are well understood, but less is known about the more common nonarteritic variety. A better understanding of variations between blood pressure and intraocular pressure could provide more information about circulation to the optic nerve head itself. Furthermore, the role of autoregulation at the optic nerve head (or lack of) as well as the role of vascular endothelium-mediated factors could play a large role in the disease. At a cellular level, axonal damage from ischemia appears to be mediated by sudden ionic shifts. A significant messenger in this process is a sodium-mediated calcium transporter which facilitates the influx of calcium ions leading to activation of proteolytic enzymes and ultimately axonal death. Various treatment options thus exist by either blocking calcium channels or inhibiting the transporter in order to prevent further axonal damage.

Intraocular pressure (IOP), which causes the lamina cribrosa to bulge backward, produces a pressure gradient along the axoplasm of exiting optic nerve axons, and challenges the circulation, interacts with presently unknown physiologic or anatomic factors to harm the optic nerve and causes loss of vision. Present treatment of glaucoma is limited to efforts to lower IOP. Future treatments may be directed at other contributing anatomic or physiologic abnormalities that permit IOP to be harmful, or at some step in the pathway from insult to mortal injury of the axon or cell body.

This review comprises a historical, clinical, and empirical examination of the dementia spectrum of depression. The primary focus of the article is to evaluate the usual dichotomy between depressive dementia as functional-reversible and degenerative dementia as organic-irreversible. It is proposed that depression, cognitive impairment, and degenerative dementia be viewed as intersecting continua. Five prototypical groups are defined along these continua: (1) major depression without depressive dementia, (2) depressive dementia, (3) degenerative dementia without depression, (4) depression of degenerative dementia, and (5) random co-occurrence of depression and degenerative dementia. The data suggest that a subset of cases of major depression without dementia appear to evolve into depressive dementia, and in turn, depressive dementia may constitute a risk factor for degenerative dementia. Depressive dementia and degenerative dementia can sometimes represent two different points of organic deterioration and severity in a long-term, multiphasic disease course; depressive dementia sometimes appears to be a transitional stage or phase in a disease progression from depression without dementia to a degenerative dementia. The concept of "transitional dementia" is introduced in a heuristic and preliminary attempt to accommodate the nosologic entity of depressive dementia.