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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brain levels of NADH and NAD+ were measured in three models of cerebral ischemia to determine whether degradation of the pyridine nucleotides is enhanced in models that generate high concentrations of lactic acid. Complete ischemia (decapitation), in which lactate increased to 14 mmol/kg, caused a gradual decrease in the NAD pool to 50% of control by 2 h. During focal ischemia (occlusion of the middle cerebral artery), the decrease in the NAD pool was less pronounced (82% of control at 2 h) despite the accentuated accumulation of lactate to 33 mmol/kg. In a third model (unilateral hypoxia-ischemia), pretreatment of animals with glucose augmented the ischemic elevation of lactate from 30 mmol/kg to 40 mmol/kg and greatly impaired restoration of energy metabolites during recirculation. However, glucose pretreatment had no effect on the size of the NAD pool during ischemia or early recovery. These results, therefore, demonstrate that the pyridine nucleotide pool is not rapidly degraded during ischemic insults that accumulate high concentrations of lactic acid. The stability of the NAD pool may have been enhanced by the limited increase in brain levels of NADH that occurred in these models of incomplete ischemia.
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PMID:Effect of lactacidosis on pyridine nucleotide stability during ischemia in mouse brain. 361 29

The effects of short- or long-term complete cerebral ischemia were studied in the gerbil brain using a multi-parameter monitoring system. Metabolic (NADH redox state) and hemodynamic responses were monitored by surface fluorometry-reflectometry. Ionic activities (K+ and pH) were measured by surface macroelectrodes. Electrical activity was evaluated by monitoring the general electrocorticogram (ECoG) as well as local DC steady potential (two sites). Two groups of gerbils were studied to compare the effects of 4-5 min occlusions with those of 30 min complete ischemia. During bilateral carotid artery occlusion the cortex is exposed to complete ischemia resulting in the complete depletion of O2 with attendant maximal reduction of NADH. Extracellular K+ began to increase as soon as energy reserves were decreased with a time course suggesting two different kinetic areas. Surface pH decreased very shortly after the occlusion. During the recovery phase, NADH was reoxidized soon after recirculation, whereas the pH and K+ recovery showed a short delay. ECoG did not recover even when all other parameters reached base-line levels. The recovery of all the measured parameters was correlated to the duration of the ischemic insult; i.e., the recovery from 30 min of ischemia took significantly longer than after 5 min of ischemia. We conclude that pH recovery depends on recirculation and adequate O2 supply to the tissue, whereas K+ recovery required not only an adequate O2 supply but also the integrity of the adenosine triphosphatase system.
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PMID:Metabolic, ionic, and electrical responses of gerbil brain to ischemia. 397 Jan 91

Temporary focal cerebral ischemia was induced in 23 cats by occluding the left middle cerebral artery (MCA) for 2 h. Animals then were divided into groups for unforced reperfusion of varying duration ranging from 2 to 48 h. Regional blood flow (rCBF) at the borders of the ischemic area was measured repeatedly using the hydrogen clearance technique, and neurological ratings were obtained, both during ischemia and reperfusion. At the scheduled end of reperfusion brains were frozen in situ with liquid nitrogen, and regional distributions of biochemical substrate contents as well as tissue pH were visualized using bioluminescence and fluorescence techniques. During focal ischemia collateral flow in the border zone dropped to 55 +/- 20.3% of control level, and all animals developed a neurologic deficit with a median of 6 points on a disability scale from 0 to 10, rCBF and functional impairment being closely correlated (tau = -0.47, P1 less than 0.005). After reopening of the MCA there was an immediate and rather uniform increase in border zone flow to 105 +/- 25.7% of control level, while neurologic recovery was quite variable. In all but one animal reversible ischemia led to persistent disturbances in the energy-producing metabolism as demonstrated by the low regional ATP content, which in part was accompanied by a diminished NADH fluorescence and an alkaline pH shift at high tissue glucose levels. These findings suggest that disturbances in cerebral energy metabolism induced by temporary ischemia may be caused by inhibition of the glycolytic pathway that is hardly reversed by unforced reperfusion and, therefore, results in permanent damage.
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PMID:Neurologic deficit, blood flow and biochemical sequelae of reversible focal cerebral ischemia in cats. 400 1

Regional lactate distribution in brain was assessed quantitatively in coronal sections using a bioluminescent technique. This bioluminescence can be induced by covering freeze-dried and heat-inactivated brain sections with a frozen solution containing enzymes and coenzymes both for lactate-dependent NADH formation and NADH-dependent bioluminescence, which was recorded photographically. Quantification and density coding of bioluminescent images were carried out by utilizing the regression coefficients of the correlation between the optical density of bioluminescent pictures and the lactate content measured in tissue samples. Regional quantitative lactate images were obtained from brain tissue taken from brain tumors or after experimental cerebral ischemia.
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PMID:Regional quantitative determination of lactate in brain sections. A bioluminescent approach. 405 29

In order to reveal the correlation of energy failure and neurotransmitter metabolism in the acute stage of incomplete cerebral ischaemia, the change of NADH (reduced form of nicotinamide adenine dinucleotide) and brain dopamine was studied histochemically using the same specimen on the unilateral carotid ligation of mongolian gerbils. The severity of clinical symptoms was well correlated with the extent and intensity of NADH fluorescence. Dopamine in the caudate nucleus on the ligated side decreased heterogeneously shortly after the cerebral ischaemia. Preservation of dopamine was noted around the small vessels with thick walls. Thus, heterogeneity of dopamine decrease appears to be closely related to the structure of microvasculature. It was seen in areas of heterogeneously increased NADH, but also in areas of its homogeneous increase within 5 to 60 min after carotid ligation. This microheterogeneity of brain dopamine may be due to the difference of perfusion pressure at the microcirculation in the acute stage of incomplete cerebral ischaemia.
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PMID:Microheterogeneity of brain dopamine in the experimental acute cerebral ischaemia. 615 6

Focal cerebral ischemia was produced in 16 cats by occluding the left middle cerebral artery (MCA) for 120 min. Cortical blood flow and pial artery pressure were determined prior to vascular occlusion and after 15, 60 and 120 min. At the end of the experiments (after 120 min MCA occlusion) heads were frozen in situ with liquid nitrogen. Cooled brains were cut into 0.5 cm thick slices. From these slices twenty-micron sections passing through the territory of the MCA were prepared in a cryostat and used in the pictorial presentation of glucose and ATP. NADH-fluorescence was recorded from the tissue slice, immersed in liquid nitrogen. In addition, tissue samples were taken from regions of interest and used for quantitative determination of biochemical substrates. In all but two animals permanent MCA occlusion led to disturbances in the energy-producing metabolism, as indicated by reduction in glucose and ATP, and increase in lactate. The regions exhibiting bright NADH-fluorescence were much smaller than those in which ATP was absent. In 6 animals NADH-fluorescence was not increased but even decreased in areas with disturbed energy-producing metabolism. A close correlation was obtained after comparing cortical blood flow measured 15 min after MCA occlusion with the area of ATP-depletion at the end of the experiments. However, the size of ATP-depletion did not correlate with flow measured 60 or 120 min after MCA occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pial arterial pressure in cats following middle cerebral artery occlusion. II. Relationship to regional disturbance of energy metabolism. 646 61

Regional changes of cerebral blood flow and biochemical substrates were assessed in the gerbil brain following different grades of cerebral ischemia. Ischemia was produced by occlusion of the right common carotid and left external carotid arteries. Gerbils were classified according to the severity of neurological symptoms as animals without, with mild and with severe neurological deficits. Brains were frozen in situ, sliced in 20-microns sections and processed for pictorial presentation of glucose and ATP, using bioluminescence techniques. Cerebral blood flow was determined in adjacent brain sections, using [14C]iodoantipyrine autoradiography. NADH fluorescence was recorded by illuminating the surface of the tissue block with ultraviolet light. Most animals without visible neurological symptoms exhibited reduced blood flow in circumscribed regions of cortex and basal ganglia of the right hemisphere without concomitant changes of biochemical substrates. In animals with mild neurological symptoms, blood flow in the right hemisphere was reduced, glucose and ATP decreased, and NADH fluorescence unhomogeneously enhanced. In animals with severe neurological symptoms blood flow was almost arrested in the right hemisphere and was distinctly reduced in the medial parts of the left hemisphere. The ischemic tissue was depleted from glucose and ATP, and exhibited bright NADH fluorescence. The severity of neurological symptoms, in consequence, correlated closely with both the degree and the size of biochemical lesions observed in the ischemic territory.
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PMID:Biochemical changes during graded brain ischemia in gerbils. Part 2. Regional evaluation of cerebral blood flow and brain metabolites. 684 58

The regional content of biochemical substrates of energy-producing metabolism was assessed in cat brains following prolonged cerebral ischemia. Ischemia was produced by intrathoracic occlusion of the innominate, the left subclavian, and both mammarian arteries, and additional lowering of the systolic blood pressure to 80 mm Hg. After 60 min of global ischemia and 3 h of recirculation, the regional distribution of glucose, ATP, and NADH was evaluated on intact brain sections by bioluminescence and fluorescence techniques. Additionally, the content of different substrates related to energy and redox state was assessed in small tissue samples. Recirculation following global ischemia led to three different patterns of biochemical substrates: in 6 of 14 animals, regional distribution of glucose, ATP, and NADH was similar to that of control animals. These animals exhibited recovery of evoked potentials and reappearance of low-voltage EEG activity. In five animals, ATP was decreased in small circumscribed regions belonging to border zones of cerebral vessels. In these regions, glucose was high and NADH-fluorescence was low, indicating that glucose deficiency was not the limiting factor for ATP depletion. In this group, evoked potentials recovered, but the EEG did not. In three animals, glucose and ATP were low throughout the whole brain, and electrophysiological recovery was absent. The pattern and localization of biochemical lesions and the correlation with hemodynamic and electrophysiological parameters suggest that disturbances of energy-producing metabolism are caused by regional ischemic episodes during the recirculation period and can be prevented by the immediate and homogeneous blood reperfusion of the brain after cerebrocirculatory arrest.
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PMID:Regional assessment of energy-producing metabolism following prolonged complete ischemia of cat brain. 687 41

Cerebral ischemia was induced in cats using bilateral carotid artery occlusion coupled with hemorrhagic hypotension. Thirty minutes of ischemia, which depleted levels of ATP and phosphocreatine throughout the cerebral cortex, was followed by 2-4 hours of recirculation. During the recovery period, cortical perfusion and NADH fluorescence were monitored through a cranial window. Postischemic perfusion, as indicated by transit time, was initially higher than control, but declined to subnormal levels by 60 minutes. NADH fluorescence transients, induced by brief anoxia, also decreased steadily during recirculation, indicating a failure of oxidation-reduction capability. The disappearance of anoxic-NADH transients usually preceded the decline of flow, suggesting that O2 delivery was not the factor limiting redox reactions. Furthermore, tissue levels of NADH, which were nearly normal after 2-4 hours of recirculation, did not indicate tissue hypoxia. In spite of normalization of NADH, resynthesis of high energy phosphates were severely impaired. The degree of ATP recovery varied widely in different cortical regions; however, there were two general groups of ATP values--one at 5% and the other at 70% of control levels. In the energy-depleted areas, NADH levels were normal, but the total pool of NAD (NADH + NAD+) and the tissue content of K+ were 43% lower than control. In contrast, the NAD pool and K+ content were only slightly diminished in the regions with greater ATP restitution. The results suggest that postischemic resynthesis of ATP may be limited not by inadequate delivery of O2, but rather by defective production of NADH.
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PMID:Factors limiting regeneration of ATP following temporary ischemia in cat brain. 706 95

We focus our attention in this presentation to the extracellular ionic changes during and after local ischemia and in repetitive versus single global ischemia. In the cat stroke model of MCA occlusion a considerable variability in the severity of ischemia was observed. This was demonstrated in electrical activity (ECoG), NAD/NADH fluoro-reflectometry and extracellular ionic changes. A striking experience was, that the K+ recovery is rather fast even after two hours of ischemia, and this is partly due to maintained activity of the sodium-potassium pump. After the MCA release a secondary acidosis occurs, which is the result of excess lactic acid production. This lactacidosis is certainly contributes to the late morphological damage. The repeated acidotic insult (in gerbil model of global cerebral ischemia) could be the cause of the more severe morphological and blood-brain-barrier damage in the repetitive ischemia too. The acidosis in many cases is even more pronounced after relieving the carotid arteries. This secondary acidosis causes endothelial damage and vasogenic oedema.
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PMID:Ion and metabolic disturbances after global and focal cerebral ischemia. 857 39


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