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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large amount of biochemical, physiological, and pharmacological data has been obtained which supports a mechanistic role of oxygen free radical-induced lipid peroxidation (LP) in post-traumatic spinal cord degeneration. Biochemical evidence of early and progressive lipid peroxidative reactions occurring in the injured spinal cord includes: an increase in polyunsaturated fatty acid peroxidation products (e.g., malonyldialdehyde), a decrease in cholesterol and the appearance of cholesterol oxidation products, an increase in cyclic GMP presumably due to free radical activation of guanylate cyclase, a decrease in tissue anti-oxidant levels (e.g., alpha tocopherol, reduced ascorbate), and inhibition of membrane-bound enzymes such as Na+ + K+-ATPase. In vitro CNS tissue studies have provided support for the possibility that LP may contribute to other early post-traumatic events including intracellular calcium accumulation and arachidonic acid release. Moreover, spinal tissue lactic acidosis, which occurs early after injury, can exacerbate LP reactions. The involvement of LP in the development of progressive post-traumatic spinal white matter ischemia has been strongly inferred from pharmacological studies in cats with known inhibitors of LP. For example, the dose-response curves for the ability of the glucocorticoid methylprednisolone (MP) to inhibit post-traumatic LP and to retard ischemia development are identical. This relationship between LP and post-traumatic ischemia is more directly implied from studies showing that pretreatment of cats with high doses of anti-oxidants (e.g., d-alpha tocopherol plus selenium p.o. or 1-ascorbic acid i.v.) can also significantly antagonize the progressive decrease in spinal cord blood flow that follows severe blunt injury. However, a similar efficacy of certain calcium and prostaglandin antagonists suggests an interrelationship between aberrant calcium fluxes, vasoconstrictor/platelet aggregating prostanoids, and LP in the post-traumatic ischemic phenomenon. In addition to a role of LP in ischemia development, the action of intensive d-alpha tocopherol and selenium pretreatment to retard anterograde cat motor nerve fiber degeneration after nerve section suggests that LP may also be a fundamental mechanism of "Wallerian" axonal degeneration after neural injury. Finally, a critical role of LP in the acute pathophysiology of CNS injury in general has been supported by the finding of an excellent correlation, in terms of efficacy and potency, between the action of glucocorticoid and nonglucocorticoid steroids to inhibit neural tissue LP in vitro and to promote early neurological recovery in severely head-injured mice.
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PMID:Role of lipid peroxidation in post-traumatic spinal cord degeneration: a review. 355 50

The clinical signs and morphological brain lesions associated with histotoxic hypoxia induced by subcutaneous injection of 3-nitropropionic acid (NPA) in rats are described, and compared to hypoxic brain damage from other causes including ischemia and hypoglycemia. The brains were perfusion-fixed with paraformaldehyde/glutaraldehyde fixative, and examined by light and electron microscopy. Intoxicated rats developed severe neurological disease characterized by somnolence, uncoordinated gait with stereotypical paddling movements, and ventral or lateral recumbency. Recumbent rats had a selective, bilaterally symmetrical pattern of severe morphological injury in the caudate-putamen, hippocampus, and thalamus. Recumbency was a consistent indicator of the development of morphological brain lesions. In contrast to reports describing rat models of ischemia and hypoglycemia, morphological injury was not seen in the cerebral and cerebellar cortices of NPA-intoxicated rats. Ultrastructurally, neuronal alterations ranged from chromatin clumping with increased cytoplasmic lucency to severe cellular shrinkage or swelling with marked mitochondrial swelling (high amplitude swelling). White matter alterations included axonal swelling and adaxonal splitting of myelin lamellae. Vascular changes included perivascular deposits of proteinaceous material presumably from leakage of serum proteins, variable electron lucency of endothelial cell cytoplasm, an apparent increase in pinocytotic vesicles, rare platelet thrombosis of capillaries, and rare intravascular blebs of luminal plasma membrane. As a model of brain damage following energy deficiency, NPA intoxication has the advantages of producing morphological brain injury in a highly predictable anatomical pattern, and at a time paralleling the onset of clinical recumbency.
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PMID:Nature and distribution of brain lesions in rats intoxicated with 3-nitropropionic acid: a type of hypoxic (energy deficient) brain damage. 356 9

Gaze-evoked amaurosis is a transient monocular loss of vision occurring in a particular direction of eccentric gaze. Six cases are reported with a mean follow-up of 5 years; three with optic nerve sheath meningiomas and three with orbital cavernous hemangiomas. Five of the six patients have had no visual deterioration during follow-up. Bilateral optic nerve sheath meningiomas led to visual deterioration in both eyes of one patient, but gaze-evoked amaurosis was present in only one eye. The symptom of gaze-evoked amaurosis, while alarming, is not predictive of permanent visual loss. Possible mechanisms for gaze-evoked amaurosis include inhibition of axonal impulses or transient optic nerve ischemia.
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PMID:Gaze-evoked amaurosis. 358 95

Microsphere embolization of rat sciatic nerve capillaries results in a central fascicular ischemic core. Twenty-four hours after microembolization, the pathological alterations along the length of 55 myelinated fibers were reconstructed by computer imaging of 2,000 serial semi-thin epoxy sections of a tissue block that extended from just above and into an ischemic core. From proximal to distal, the typical sequence of pathological alterations was: normal----swollen dark axons + thin myelin or demyelination----attenuated axons----axon cytolysis (46 fibers) or normal axons (9 fibers). Because organelle accumulation and axonal swelling were the earliest and most proximal pathological lesions, we infer that regional hypoxia causes axonal stasis as a primary event. Demyelination was found in fibers showing swollen dark and attenuated axons. These findings suggest that axons are selectively vulnerable to acute ischemia and that, depending on severity, the fibers either undergo axonal degeneration or transitory structural alterations without axonal degeneration, the latter consisting of axonal changes and secondary demyelination.
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PMID:Acute ischemia causes axonal stasis, swelling, attenuation, and secondary demyelination. 367 96

Injection of low-dose arachidonic acid into the rat femoral artery occludes the vasa nervorum of the tibial nerve and produces focal and generalized ischemia with transient effects on nerve conduction. Across a severely ischemic segment of the proximal tibial nerve there is a marked fall in amplitude of the compound muscle action potential (CMAP), indicating focal conduction block. There is also significant slowing of maximal motor conduction velocity (MCV) through this nerve segment, but no dispersion of the proximally elicited response. Distally, in a region of less severe ischemia, there is mild slowing of MCV, but no further decrement in the CMAP amplitude. The conduction block begins 5-15 minutes after injection, reaches a nadir at 30 minutes, and persists in more severe cases for at least 2 hours. Despite these prolonged electrophysiologic abnormalities, there is no evidence of axonal degeneration or segmental demyelination.
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PMID:Transient focal conduction block following experimental occlusion of the vasa nervorum. 371 40

Acute, graded, nerve compression was applied to the sciatic nerves of 91 rats in whom an inflatable miniature Plexiglass compression device had been implanted in the thigh. The experiment was designed to study the pathogenesis of lesions in the nerve entrapment syndrome. Under general anesthesia, external pressures of 80 mm of Hg, 30 mm of Hg and 10 mm of Hg were used to compress nerves for 2 hours. Identical compression devices were placed around the contralateral sciatic nerves but remained uninflated so that these nerves could be used as controls. Nerves were excised at intervals of 4 and 24 hours, and at 1, 2, 5, 6, 7, 10, 14, and 28 days, and full thickness transverse sections were made from Araldite blocks. The first pathologic change was nerve edema which was observed at all time points and correlated with the severity of axonal injury. Axonal lesions were predominant in nerves exposed to 80 mm of Hg (7.5 +/- 1.9 nerve fibers per high power microscopic field (HPF)) while nerves compressed at 30 mm of Hg showed fewer damaged axons (2.6 +/- 1.4 per HPF). Demyelination was the predominant lesion in nerves subjected to 30 mm of Hg and was commonly present in nerves around which the compression chamber remained uninflated. Electron microscopy revealed demyelination to be associated with Schwann cell necrosis. The topography of nerve fiber injury was remarkable; subperineurial fibers were often damaged after compression of nerves in which nerve fibers at the core of the fascicle remained unaffected. The findings suggest that local external compression causes ischemia in nerve fibers served by transperineurial vessels, with severe compression causing axonal damage, while lesser degrees of compressive injury are associated with demyelination.
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PMID:Pathology of experimental nerve compression. 372 67

The superficial peroneal nerve was taken from 12 arteriosclerotic non-diabetic patients just after amputation of a leg. Preparations of teased fibers were performed in 8 cases. Specimens were studied by light and electron microscopy in all cases. Histograms of myelinated fibers in transverse semi-thin sections showed that depletion of myelinated fibers varied from case to case, with no selective vulnerability in either the large or the small diameter group. There was a dramatic loss of myelinated fibers in only one case. No real nerve infarct was observed. In most cases, regions of Wallerian-like degeneration were prevalent; however, myelino-axonal changes were severe only in a few cases. Axons with organelle aggregates were seen in some cases. Figures of segmental demyelination were not numerous in this series. Unmyelinated fibers were also damaged, and the degree of involvement differed from case to case. Pathological changes observed in this study confirm the relative resistance of peripheral nerve to ischemia.
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PMID:Quantitative, histological and ultrastructural studies of peripheral nerve in arteriosclerotic non-diabetic patients. 379 29

The time course of structural change in epilepsy-induced necrosis of the substantia nigra was studied by light and electron microscopy, and was correlated with previous metabolic studies. By light microscopy, tinctorial pallor appeared early, followed by pan-necrosis and macrophage infiltration. Mild lesions showed neuropil vacuolation but sparing of neurons, rather than a selective neuronal vulnerability. Electron microscopy of the evolving necrosis revealed an orderly sequence of structural damage involving first axons, then dendrites, neurons, and glia. No necrotic endothelial cells could be found, even in areas of apparent pan-necrosis by light microscopy. Pericytes near the vascular lumen were spared, whereas those in outer locations were necrotic. Edema, measured densitometrically, was absent. Previous metabolic studies of this lesion have demonstrated a pronounced focal lactic acidosis due to anaerobic hypermetabolism. Although the lesions resemble infarcts, hypermia rather than ischemia has been shown to accompany their development. Structural preservation of endothelial cells and inner pericytes likely stems from proximity to the moving blood stream, away from the site of lactic acid production in the neuropil. The findings indicate that the perfusion of necrotic tissue occurs via a persisting, intact microcirculation. The relative neuronal sparing and the early axonal rather than dendritic lesion show a clear distinction from excitotoxic pathology.
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PMID:Early axonal lesion and preserved microvasculature in epilepsy-induced hypermetabolic necrosis of the substantia nigra. 379 37

In an ischemia-induced model of an acute motor neuron disorder, there is anterior horn cell damage with Wallerian degeneration in ventral roots; dorsal root ganglia and dorsal roots are unaffected. In a mixed nerve there is axonal degeneration reflecting loss of motor fibers. The sural nerve is normal showing that it does not contain motor fibers. This observation is relevant to the neuropathology of motor neuron disease where axonal degeneration found in the sural nerve suggests involvement of sensory fibers.
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PMID:Motor fibers in the sural nerve. 379 47

Accelerated renovascular hypertension produces optic nerve changes ranging from optic disc edema to optic atrophy. To elucidate the pathogenesis of hypertensive optic neuropathy, the optic nerves from 12 monkeys (23 eyes) with accelerated renovascular systemic hypertension were studied by electron and light microscopy. Within 21 months, the animals demonstrated the entire spectrum of pathologic changes. In the optic nerves with optic disc edema, the prelaminar optic nerve exhibited vasoconstriction with subsequent axonal hydropic swelling, axolemma disruption, and glial swelling. In retrolaminar myelinated optic nerve, vasoconstriction was more severe, with endothelial swelling and pericytic degeneration resulting in intramyelinic vacuoles and glial swelling. Optic disc edema appeared to result from axonal hydropic swelling secondary to ischemic infarct, followed by loss of axons and gliosis in the prelaminar optic nerve. The retrolaminar myelinated nerve showed prominent microglial reaction and eventual atrophy of axons and glia. Ischemia seemed to play a major role in hypertensive optic neuropathy, which represents anterior ischemic optic neuropathy.
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PMID:Fundus lesions in malignant hypertension. II. A pathologic study of experimental hypertensive optic neuropathy. 402 51


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