Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new experimental model of focal peripheral nerve infarction is presented. Ischemia was produced in 12 rats by intravascular thrombosis induced by the photochemical reaction of systemically injected rose bengal to the local application of light from a cold light source. Clinical, electrophysiological and immunohistochemical techniques were used to monitor the pathology and the time course of experimental ischemic neuropathy (EIN) of the sciatic nerve. Primary axonal neurofilament disintegration was detectable 4-24 h after illumination and was followed by wallerian degeneration within the first week. At 7 days, there was a secondary disruption of myelin sheaths accompanied by massive infiltration of macrophages and phagocytosis of the necrotic debris. The majority of detected macrophages were derived from circulating blood monocytes which had invaded the nerve. Two weeks after the initial lesions, degeneration had advanced without any signs of regeneration or remyelination. Electrophysiological recordings corroborate the findings of primary axonal degeneration and failure of regeneration up to 2 weeks after the lesion.
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PMID:Photochemically induced experimental ischemic neuropathy: a clinical, electrophysiological and immunohistochemical study. 841 69

Posttraumatic ischemia appears to be largely responsible for the extension of lesions in acute injury of the spinal cord. In the present study, we have evaluated the putative improvement of axonal function by the calcium channel blocker nimodipine after acute trauma of the spinal cord. Three techniques were used: (1) spinal cord blood flow (SCBF) using a scanographic technique with stable xenon, (2) somatosensory evoked potentials (SEPs), and (3) magnetic resonance imaging (MRI). Thirteen baboons were used in this study. Acute trauma was achieved by compression of the spinal cord at level L1 by applying pressure for 5 sec with an inflated balloon catheter injected with Ringer's solution. Following the injury, one group (n = 5) received a saline infusion (placebo) for seven days, and a second group (n = 8) received a nimodipine infusion (0.04 mg/kg/h) during the same period of time. SCBF and SEP were first recorded prior to trauma. SCBF, SEPs, and MRI were then recorded on the day of the injury and eight days prior to histologic examination of the spinal cord. In these studies nimodipine significantly improved SCBF. The decrease in SCBF observed at day one and day eight following trauma was significantly reduced in the treated group. Two baboons in the treated group also showed improvement of axonal function as assessed by SEP. No significant difference was observed with MRI, however, histologic study revealed that the lesions were significantly smaller in the treated group. Based on these observations we conclude that a week of nimodipine treatment following spinal cord injury enhances SCBF, limits the size of the spinal cord lesion, and perhaps improves functional recovery.
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PMID:Effects of nimodipine on posttraumatic spinal cord ischemia in baboons. 841 Dec 20

It is possible to learn more about peripheral nerve function in human subjects than is obtainable with routine nerve conduction studies, and thereby to study the basis of "positive" symptoms, such as paresthesias. Using microneurography, ectopic impulse activity in cutaneous afferents has been recorded in patients suffering from neurologic disorders and in normal subjects in whom paresthesias were provoked by hyperventilation, prolonged tetanization of cutaneous nerves and ischemia. Using relatively simple modifications of standard nerve conduction techniques, the increases in axonal excitability responsible for this ectopic activity have been documented in human volunteers. Hyperventilation increases axonal excitability but does not change supernormality, probably because Na+ channels are activated by the decrease in [Ca2+] on the axonal membrane. Prolonged tetanic stimulation and ischemia probably share similar mechanisms. At least in motor axons, postischemic ectopic activity occurs when the hyperpolarization that results from activation of the Na+/K+ pump lowers the membrane potential below the equilibrium potential for K+. A high extracellular [K+] can then result in an inward current producing depolarization and possibly triggering regenerative processes.
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PMID:Microneurography, impulse conduction, and paresthesias. 841 55

By taking advantage of the specific neuronal and connective organization of the hippocampus and the different susceptibility of hippocampal neurons to transient cerebral ischemia or intraventricular injections of kainic acid (KA), we examined the microglial reactions to different types of neuronal injury. In all areas with neuronal or axonal degeneration, the microglial cells reacted by specific degeneration-related morphological transformations and expression of class I major histocompatibility complex (MHC) antigen. Subpopulations of microglial cells also expressed class II MHC antigen and leukocyte common antigen (LCA) in relation to (1) degenerating nerve cell bodies in the dentate hilus and the CA1 and CA3 pyramidal cell layers, (2) postischemic degeneration of dendrites in the stratum radiatum of CA1, and (3) combined dendritic and axonal degeneration in the stratum radiatum of the KA-lesioned CA3. MHC II and LCA expression was not observed in relation to degeneration of the CA3-derived Schaffer collaterals in CA1 after KA-induced CA3 lesions. In the case of ischemia the degeneration-related reactions were preceded by an early, generalized microglial reaction, which also included areas without subsequent signs of neural degeneration. This reaction, which was transient and characterized by subtle morphological changes and induction of class I MHC antigen only, was presumably triggered by a general postischemic perturbation of the cerebral microenvironment, and not by actual neural degeneration. In conclusion, we found that microglial expression of class I MHC antigen was a sensitive marker of both the general perturbation after ischemia and axonal degeneration distant from the areas of actual nerve cell death.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus. 842 61

Over the past 15 years, neuropathological studies, patient monitoring, and data emerging from the laboratory have significantly advanced the understanding of both primary and secondary brain damage. The challenge now rests with the clinician treating head injury, who must translate these recent developments into real benefits for the patient. Neurological deterioration after head injury may be due to the effects of secondary mechanisms in up to one-third of cases. These secondary events may follow early insults such as transient global ischemia, hematomas, or diffuse axonal injury. They may be mediated by complex cascades of biochemical processes. Many of these secondary posttraumatic events have been targeted as potential sites for pharmacological intervention. In models of focal brain ischemia, a new generation of compounds that inhibit activity of glutamate has been shown to ameliorate the severity of the ischemic insult. Other potential neuroprotective agents that are currently being clinically investigated include free radical scavengers and calcium antagonists. Preliminary findings show indications of improved neurological outcome with early administration of a number of these drugs. Because head-injured patients tend to be admitted to the hospital within hours of injury, which allows for pretreatment or early therapy, several ongoing trials are assessing safety, tolerance, and efficacy of many new therapeutic agents combined with standard management. It is hoped that the outcome of this novel approach to head injury management will be positive and will help to reduce the high morbidity and mortality associated with head injuries.
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PMID:Opportunities for neuroprotective drugs in clinical management of head injury. 844 99

Head injuries vary widely in their etiology, pathophysiology, clinical presentation, and optimal treatment strategies. Broadly speaking, there are two categories of brain injury: focal injuries and diffuse injuries. Focal brain injuries, which are usually caused by direct blows to the head, comprise contusions, brain lacerations, and hemorrhage leading to the formation of hematoma in the extradural, subarachnoid, subdural, or intracerebral compartments within the head. Diffuse brain injuries, which are usually caused by a sudden movement of the head, comprise classical brief cerebral concussion and more prolonged posttraumatic coma, also known as diffuse axonal injury. Primary traumatic effects involve neural or vascular elements of the brain, which can be affected by delayed effects such as deafferentation or secondary events such as ischemia, swelling, cerebral edema, and increased intracranial pressure. Axonal damage at the node of Ranvier results in a traumatic defect in the axonal membrane that causes the excessive accumulation of calcium ions within the intracellular compartment of the axon. Brain ischemia can result in a similar effect, further increasing the accumulation of calcium ions, which can lead to axonal degeneration. Injury-specific treatments are now being designed to alter the various pathophysiological mechanisms of brain injury.
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PMID:Mechanisms of brain injury. 844 4

The microtubule-associated protein tau plays an important role in the dynamics of microtubule assembly necessary for axonal growth and neurite plasticity. Ischemia disrupts the neuronal cytoskeleton both by promoting proteolysis of its components and by affecting kinase and phosphatase activities that alter its assembly. In this study the effect of ischemia and reperfusion on the expression and phosphorylation of tau was examined in a reversible model of spinal cord ischemia in rabbits. tau was found to be dephosphorylated in response to ischemia with a time course that closely matched the production of permanent paraplegia. Dephosphorylation of tau was limited to the caudal lumbar spinal cord. In a similar manner, Ca2+/calmodulin-dependent kinase II activity was reduced only in the ischemic region. Thus, dephosphorylation of tau is an early marker of ischemia as is the rapid loss of Ca2+/calmodulin-dependent kinase II activity. tau, however, was rephosphorylated rapidly during reperfusion at site(s) that cause a reduction in its electrophoretic mobility regardless of the neurological outcome. Alterations in phosphorylation or degradation of tau may affect microtubule stability, possibly contributing to disruption of axonal transport but also facilitating neurite plasticity in a regenerative response.
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PMID:Changes in phosphorylation of tau during ischemia and reperfusion in the rabbit spinal cord. 852 66

We observed incidentally that rat sciatic nerve in contact with oxidized cellulose (OC), an absorbable hemostatic agent, underwent focal fiber degeneration, and we undertook studies to determine the mechanism of its production. Topically applied OC generated acute nerve damage within the adjacent nerve fascicle of rat sciatic nerve in a dose-dependent fashion (r = 0.99, P < 0.01, threshold amount: 9.9 mg). IN single teased fibers, the predominant type of myelinated fiber damage was axonal degeneration. The subperineurial blood flow of the rat sciatic nerve was serially measured by microelectrode hydrogen polarography, and the reduction at 90 min after application of OC was not greater than that of controls. A thin polyethylene membrane interposed between OC and the sciatic nerve almost completely prevented the nerve damage. These data suggest that the chief mechanism of nerve damage by OC was neither compression nor ischemia, but was a diffusible chemical mechanism. Care should be taken to avoid direct OC application around peripheral nerves.
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PMID:Oxidized cellulose causes focal neuropathy, possibly by a diffusible chemical mechanism. 852 2

Although the neuropathology of ischemic fiber degeneration (IFD) is relatively well known, its pathogenesis is poorly understood. One putative mechanism of IFD is oxidative stress, causing a breakdown of the blood-nerve barrier (BNB) and lipid peroxidation. We evaluated the effect of ischemic reperfusion of rat sciatic-tibial nerve seeking biochemical and pathologic evidence of BNB disruption and lipid peroxidation. Ischemia, caused by the ligation of the supplying arteries to sciatic-tibial nerve, was maintained for 3 h, followed by reperfusion. Reperfusion resulted in an increase in nerve lipid hydroperoxides, greatest at 3 h, followed by a gradual decline over the next month. Nerve edema and IFD consistently became more severe with reperfusion, indicating that oxidative stress impairs the BNB (edema) and causes IFD. Reduced reperfusion was greatest over distal sciatic nerve and midtibial nerve at day 7. The most ischemic segment (midtibial), of nonreperfused ischemic nerves (duration 3 h), underwent both edema and IFD that was as pronounced as those of other segments after reperfusion, and underwent a smaller increase with reperfusion, suggesting that ischemia alone can also cause IFD and edema. The type of fiber degeneration was that of axonal degeneration.
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PMID:Ischemic reperfusion causes lipid peroxidation and fiber degeneration. 853 68

Severe traumatic brain injuries are extremely heterogeneous. At least seven of the secondary derangements in the brain that have been identified as occurring after most traumatic brain injuries also occur after cardiac arrest. These secondary derangements include posttraumatic brain ischemia. In addition, traumatic brain injury causes insults not present after cardiac arrest, i.e., mechanical tissue injury (including axonal injury and hemorrhages), followed by inflammation, brain swelling, and brain herniation. Brain herniation, in the absence of a mass lesion, is due to a still-to-be-clarified mix of edema and increased cerebral blood flow and blood volume. Glutamate release immediately after traumatic brain injury is proven. Late excitotoxicity needs exploration. Inflammation is a trigger for repair mechanisms. In the 1950s and 1960s, traumatic brain injury with coma was treated empirically with prolonged moderate hypothermia and intracranial pressure monitoring and control. Moderate hypothermia (30 degrees to 32 degrees C), but not mild hypothermia, can help prevent increases in intracranial pressure. How to achieve optimized hypothermia and rewarming without delayed brain herniation remains a challenge for research. Deoxyribonucleic acid (DNA) damage and triggering of programmed cell death (apoptosis) by trauma deserve exploration. Rodent models of cortical contusion are being used effectively to clarify the molecular and cellular responses of brain tissue to trauma and to study axonal and dendritic injury. However, in order to optimize therapeutic manipulations of posttraumatic intracranial dynamics and solve the problem of brain herniation, it may be necessary to use traumatic brain injury models in large animals (e.g., the dog), with long-term intensive care. Stepwise measures to prevent lethal brain swelling after traumatic brain injury need experimental exploration, based on the multifactorial mechanisms of brain swelling. Novel treatments have so far influenced primarily healthy tissue; future explorations should benefit damaged tissue in the penumbra zones and in remote brain regions. The prehospital arena is unexplored territory for traumatic brain injury research.
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PMID:Resuscitation from severe brain trauma. 860 6


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