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

It has been proposed that lithium ion desensitizes neuronal receptors that function via the inositol phospholipid signaling mechanism. We examined the effects of lithium chloride on the morphologic outcome after 5 minutes of cerebral ischemia induced in gerbils by occluding both common carotid arteries under brief halothane anesthesia. In three treated groups of 10 gerbils each, 5 meq/kg i.p. lithium chloride was given 2 days, 1 day, and 2 hours before ischemia; 2 hours before ischemia; or immediately after the end of ischemia. Corresponding control groups of nine or 10 gerbils each received equivalent volumes of saline injected at comparable times. All gerbils were perfusion-fixed 1 week later, and neuronal density of the hippocampal CA1 pyramidal cells was determined. Lithium induced very mild intraischemic systemic hypothermia, but postischemic hyperthermia developed in both treated and control groups. Neuronal densities were equal in corresponding groups. The results indicate that our regimen of lithium administration provides no benefit in survival of hippocampal neurons, and intraischemic hypothermia of less than 0.8 degrees C is not protective. Other strategies to inactivate the signal transduction system that is specific for excitatory neurotransmission should be evaluated.
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PMID:Lithium ion does not protect brain against transient ischemia in gerbils. 184 49

This study examined regional patterns of increased vascular permeability and morphological indicators of acute neuronal injury following normothermic and mildly hyperthermic forebrain ischemia. Rats underwent 20 min of four-vessel occlusion during which intraischemic brain temperature was maintained at either 37 degrees C or 39 degrees C. At 45-min recirculation, the blood-brain barrier (BBB)-tracer horseradish peroxidase was injected and rats were perfusion-fixed at 1-h recirculation for light and electron microscopic analysis. In normothermic and hyperthermic rats, sites of increased vascular permeability were spatially correlated with dark shrunken type IV neurons. Neuronal alterations within cortical, hippocampal, striatal, and thalamic areas ranged from mild cytoplasmic vacuolation and mitochondrial swelling to severe cytoplasmic shrinkage and increased density. Although dark shrunken neurons were routinely associated with permeable blood vessels in both temperature groups, dark neurons were not detected in regions demonstrating an intact BBB. Following normothermic brain ischemia, the appearance of dark shrunken neurons was restricted to the cerebral cortex and striatum. In both temperature groups, luminal leukocytes were detected within otherwise well-perfused forebrain microvascular beds. Our studies suggest a close interrelationship between postischemic microvascular abnormalities, including increased vascular permeability, and morphological indicators of acute neuronal injury following brain ischemia.
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PMID:Interrelationships between increased vascular permeability and acute neuronal damage following temperature-controlled brain ischemia in rats. 188 38

Neuronal vulnerability to ischemia in the rat hippocampus was investigated by the measurement of high potassium evoked overflow of neurotransmitters using in vivo microdialysis. Changes in the extracellular level of amino acids caused by high potassium (100 mM) stimulation were measured on the 5th day after 20 min of forebrain ischemia, and the ratio of stimulated to basal levels or the peak concentration following the stimulation were correlated to neuronal activities. The responses to high potassium stimulation of glutamate and aspartate were reduced to 35-40% of the control values on the 5th day after 20 min ischemia, whereas the responses of gamma-aminobutyric acid (GABA) and taurine were not reduced on the 5th day after the ischemia. These results suggest that excitatory amino acid neurons (glutamatergic and aspartatergic) are more vulnerable than inhibitory amino acid neurons (GABAergic and taurinergic) in the hippocampus. Histologically, hippocampal CA1 pyramidal cells, which are believed to be glutamatergic or aspartatergic, demonstrated a marked neuronal necrosis on the 5th days after 20 min ischemia. Biochemical features revealed by high potassium stimulation may be an expression of 'delayed neuronal death' in the hippocampal CA1 area.
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PMID:Ischemic neuronal injury in the rat hippocampus following transient forebrain ischemia: evaluation using in vivo microdialysis. 190 77

Overdistraction and derotation of the scoliotic spine during surgery represent potential complications that could lead to spinal cord dysfunction and paralysis. Neuronal loss and, consequently, the inability to regain function may be attributable to primary damage (eg, mechanical), secondary cell death (eg, such as that produced by ischemia) or a combination of both. Beyond intraoperative recognition and removal of the rods, effective strategies to prevent this neuronal loss have yet to be developed. This emphasizes the need for a clearer understanding of the molecular events that contribute to neuronal injury in the central nervous system. Considerable evidence has indicated that the excitatory transmitter L-glutamate and the N-methyl-D-aspartate (NMDA) excitatory amino acid receptor may contribute to the secondary neuronal death observed in a wide variety of neurological insults, including ischemia. The current investigation was undertaken to elucidate the potential role of the NMDA receptor in spinal cord pathology. Isolated rat spinal cords were exposed to anoxic physiologic solutions in the presence and absence of Ca++, NMDA receptor agonists, and a noncompetitive NMDA receptor antagonist. The extent of neuronal damage was assessed by quantitating the degradation of the cytoskeletal neurofilament protein. A substantial increase in the loss of neurofilament protein was observed in spinal cords exposed to anoxic conditions in the presence of Ca++ as compared with the absence of Ca++. Exposure to excitatory amino acid agonists (L-glutamate or NMDA) further potentiated the degradation of the neurofilament protein; an effect that was reversed by a noncompetitive NMDA receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Excitotoxins can produce protein degradation in the spinal cord. 197 92

The purpose of the present study was to determine the consequences of postischemic neuronal damage on CMRglc. Forebrain ischemia of 10 min duration was induced in male Wistar rats. The extent of neuronal damage and the numbers of immunocytochemically detected astrocytes in the hippocampal CA1 subfield as well as CMRglc were determined 2, 5, 7, and 14 days after ischemia. CBF was additionally measured 7 days postischemia. CMRglc was decreased in cortical and thalamic structures up to 5 days postischemia, and was normalized again on day 7 after ischemia. In the hippocampal areas, CMRglc was decreased only on day 2 after ischemia, was normalized after 5 days, and increased in the stratum oriens and pyramidale of the CA1 subfield from postischemic day 7 onward. Neuronal damage was clearly demonstrable 5 days after ischemia and further increased up to day 7. The number of GFAP-reactive astrocytes increased markedly at day 7 postischemia. It is assumed that the activation of astrocytes is induced by neuronal damage, and that the astroglial metabolism is responsible for the increase in CMRglc of the CA1 subfield 7 days after ischemia. The decrease in CBF of the CA1 subfield 7 days after ischemia could be caused by a reduced density of perfused capillaries.
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PMID:Postischemic neuronal damage causes astroglial activation and increase in local cerebral glucose utilization of rat hippocampus. 198 94

An autopsied patient with Menkes' kinky hair disease, who showed unusually long survival until the age of five years with typical neuropathological changes, was examined for distribution of neuronal depletion in the cerebral cortex, and the cerebellar changes were compared morphologically and immunohistochemically with those found in a younger patient (1 year 8 months old) reported previously. Neuronal loss in the cerebral cortex in the both cases, which was ill-defined and unassociated with gliosis, was preferentially distributed in the fifth and sixth layers, especially of the gyral bottom in almost all lobes in the older case. Therefore, this change was thought to be secondary to local ischemia caused by mechanical distortion at the stage of gyrus formation in addition to abnormal development. Ultrastructurally, a prominent increase of confronting cisternae (CC) complexes was found in the perikaryon and processes of Purkinje cells in both cases, and in the older patient CC complexes were arranged more densely and were transformed into concentric lamellar structures in the swollen dendrites. Immunohistochemically, the stainability of neurofilaments (NF, 200 kDa) in Purkinje cells, with or without somatic sprouts was faint or negative in the older patient compared with the marked or moderate positivity in the younger patient and age-matched controls. Empty baskets were absent and NF-positive axonal terminals and synaptophysin-positive granules on Purkinje cells were markedly decreased in both cases. These changes suggest that Purkinje cells degenerate progressively with time and that basket cells also are simultaneously involved.
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PMID:Menkes' kinky hair disease: morphological and immunohistochemical comparison of two autopsied patients. 202 48

The effect of cycloheximide, a protein synthesis inhibitor, on hippocampal selective neuronal death was morphologically studied in rats subjected to 10 min forebrain ischemia using a 4-vessel occlusion model. Neuronal damage in the hippocampal CA1 subfield 72 h after ischemic insult was dramatically decreased by the lasting inhibition of protein synthesis through consecutive administration of cycloheximide. Cycloheximide, which was administered once within the first 24 h of recirculation, showed protective action on ischemic cell necrosis and its most potent effect was observed when injected at 12 h of post-ischemia. After 36 h of recirculation, however, treatment with cycloheximide could no longer prevent cell death. The possibility is considered that hippocampal delayed neuronal death following transient ischemia is caused by abnormal protein(s).
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PMID:Effects of cycloheximide on delayed neuronal death in rat hippocampus. 207 92

Previous therapeutic studies on the prevention of selective vulnerability of neurons in the hippocampus have suggested that the critical period for induction of delayed neuronal injury occurs early during recirculation. To determine the onset and duration of this period, an ultrashort-acting barbiturate (methohexital) was infused into the left carotid artery of 47 gerbils after various times of recirculation following 10 minutes of bilateral forebrain ischemia. Neuronal density in the left CA1 sector was determined 7 days later by counting the number of surviving neurons per millimeter of pyramidal cell layer. In 16 saline-treated gerbils, less than 10% of the CA1 neurons survived the 10 minutes of ischemia. Postischemic carotid infusion of methohexital improved neuronal survival, the degree of improvement depending on the timing and duration of the methohexital infusion. When carried out during the initial 40 minutes of recirculation, methohexital infusion for 10 minutes increased the number of surviving neurons to approximately 60% of that in five sham-operated control gerbils. This increase was significant for infusions carried out between the 10th and 20th minutes (n = 6, p less than 0.05) and between the 30th and 40th minutes (n = 6, p less than 0.05) of recirculation. Methohexital infusion for 20 minutes increased neuronal survival to 95% and 73% of that in the controls when carried out between the 0th and 20th minutes (n = 5, p less than 0.005) and between the 20th and 40th minutes (n = 5, p less than 0.005) of recirculation, respectively. Protection was nonsignificant for 10- or 20-minute methohexital infusions carried out after the 40th minute of recirculation. Our results demonstrate that the pathologic processes leading to delayed neuronal injury in the CA1 sector are induced during the initial 40 minutes of recirculation and that barbiturates are able to reverse these processes only if given during this period.
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PMID:Therapeutic window of CA1 neuronal damage defined by an ultrashort-acting barbiturate after brain ischemia in gerbils. 221 15

U78517F is a novel inhibitor of iron-catalyzed lipid peroxidation that combines the tetramethylchroman antioxidant ring portion of alpha-tocopherol with the amine of the previously described 21-aminosteroids (e.g., U74006F). U78517F inhibited 200 microM FeCl2-initiated lipid peroxidation in rat brain homogenates by 50% at a concentration of 0.6 microM compared with 8 microM for U74006F, 28 microM for alpha-tocopherol, and 43 microM for the ring portion of alpha-tocopherol (i.e., trolox). U78517F is devoid of hypothermic or antiexcitotoxic actions or interactions with known neurotransmitter receptors. When administered intraperitoneally to male gerbils at 10 minutes before and again at the end of a 3-hour period of unilateral carotid artery occlusion, U78517F decreased 24-hour postischemic cortical neuronal necrosis. Neuronal density in the medial portion of the cortex was increased from 34.2% of normal in vehicle-treated animals to 86.3% in the U78517F-treated animals. In the lateral cortical area, the vehicle group showed only 3.3% neuronal survival versus 48.2% in the drug-treated group. In a separate series of experiments with the same focal ischemia model, identical dosing with U78517F enhanced the postischemic recovery of cortical extracellular calcium without any effect on ischemic or postischemic cortical blood flow. The effect on calcium recovery was observed at intraperitoneal doses as low as 0.1 mg/kg. The compound also was effective in partially attenuating 1-week postischemic hippocampal CA1 neuronal loss in a gerbil global ischemia model involving brief (15-minute) bilateral carotid occlusion, but sustained dosing was required. These results document the anti-ischemic efficacy of a novel and potent inhibitor of iron-catalyzed lipid peroxidation and further support a key role of oxygen radicals in postischemic brain damage.
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PMID:Nonsteroidal lazaroid U78517F in models of focal and global ischemia. 223 90

We have developed a functional vegetative model by an 18-min clamping of the ascending aorta combined with a bypass formation between the aorta to right atrium and the aorta to femoral vein. Complete global brain ischemia (CGBI) induced for 18 min with this model provided the following distinct advantages: cardiopulmonary functions were well preserved during postischemic recirculation, and all dogs survived without serious extracerebral complications. Neuronal damage in vegetative dog induced by an 18-min CGBI was studied by light and electron microscopy. The Purkinje cells and the hippocampal CA1 pyramidal cells showing clumping of nuclear chromatin and slightly increased stainability were observed after CGBI without recirculation. All these neurons showed transient increased stainability with microvacuolation 15 min after recirculation. Over 50% of these neurons showed virtually normal features 1 h after recirculation. Damage to these neurons progressed again slowly up to 6 h after recirculation. However, all these neurons had disintegrated 2-3 days after recirculation. A decrease in synaptic vesicles was observed in many presynaptic terminals in the molecular layers of the cerebellum after CGBI without recirculation. These changes in the presynaptic terminals progressed 15 min after recirculation. These results indicated that the damage to the Purkinje cells and the CA1 pyramidal cells induced by CGBI consisted of two phases, and that the change in the early phase was reversible. We speculate that the damage to the Purkinje cells in the early stage is related to the decrease of the synaptic vesicles in the presynaptic terminals.
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PMID:Histological changes of neuronal damage in vegetative dogs induced by 18 minutes of complete global brain ischemia: two-phase damage of Purkinje cells and hippocampal CA1 pyramidal cells. 225 10


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