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

Brain ischemia causes a large variety of cellular and tissular disturbances that can lead to cerebral infarction. A lack of glucose and oxygen supply that is constantly needed for normal brain function produces a lesion becoming more severe as the duration of the ischemic period increases. Experimental models allow to examine the effect of permanent versus transient ischemia with reperfusion. Cellular and tissular ischemic disturbances can, to a certain extent, be separated from those occurring at reperfusion. Ischemia causes severe and at times non-recoverable alterations, suggesting that minimizing the duration of ischemia by favoring recanalization would be clinically desirable. However, many alterations occurring at reperfusion time do also favor lesion progression. Certain surviving neurons at the penumbra region can become affected during reperfusion as the infarct progresses. Reperfusion injury seems to offer a comparatively larger window for therapeutical intervention aimed to protect cells from death. Several postischemic changes such as alteration of cell membranes, induction of heat shock protein (Hsp70) and protein synthesis inhibition are considered here, together with putative pharmacological treatments directed to reduce or arrest postischemic lesion progression.
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PMID:[Cell membrane alterations and protein synthesis in experimental models of cerebral ischemia: pharmacological implications in the treatment of ischemic disease]. 947 Nov 79

To study the effects of glutamate transporters on the pathogenesis of brain infarct, pharmacological and histological analyses were carried out on the thrombotic focal ischemic model. Expression of mRNA coding for the glutamate transporter GLAST increased significantly in the penumbra at 72 h following the ischemia. Combined with confocal laser scanning microscopic analysis, double staining showed expression of GLAST mRNA in both neurons and glial cells in the penumbra. L-trans-Pyrrolidine-2,4-dicarboxylate (L-trans-PDC), a glutamate uptake inhibitor, dose-dependently enhanced the volume of the infarct induced by the ischemia. The results suggest that a compensatory increase in the activity of glutamate transporter may accompany pathological changes after ischemic injury.
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PMID:Effect of glutamate transporter on neuronal damage induced by photochemical thrombotic brain ischemia. 951 87

According to an epidemiological study of cerebrovascular disease carried out in China in 1986, the prevalence, incidence, and mortality rates were 159.93/100,000, 115.61/100,000, and 31.33/100,000, respectively. These figures were high compared to available epidemiological data for the rest of the world. This highlights the fact that, as in other countries, functional rehabilitation after stroke is an important medical and social need in China. Clinical experience shows that within a few hours to a few months after a stroke, a large proportion of patients spontaneously experience partial, or on occasion, complete recovery from neurologic symptoms. However, functional rehabilitation in medical care units is required because it assists in and accelerates the recovery of impaired function. Almitrine-raubasine has been used to improve functional rehabilitation after stroke for some time in China. By enriching the oxygen content of arterial blood, it brings more oxygen to the cerebral tissues and therefore promotes cerebral aerobic metabolism during ischemia. In the acute phase of stroke, positron emission tomography showed, in man, that almitrine-raubasine helps normalize the ischemic penumbra area, as shown by an improvement in the coupling between oxygenation and perfusion. Long after stroke, single photon emission computed tomography showed that almitrine-raubasine restores normal cerebral vasodilator response to acetazolamide. With a view to further documenting the clinical efficacy of almitrine-raubasine on the convalescent period of patients with cerebrovascular disease, a double-blind, placebo-controlled study is planned. One hundred patients with ischemic cerebrovascular disease in the territory of the carotid artery will be included 4-6 weeks after the acute onset. Two tablets daily of almitrine-raubasine or placebo will be prescribed for 3-6 months. Before treatment, there will be a 2-week washout period for all other drugs, except for antihypertensive and antidiabetic drugs. In addition to complete clinical monthly examinations, neurological functional deficit scores, Barthel index, Hasagawa Dementia scales, and CT scan are scheduled. The study results should confirm those reported in the scientific literature: although untreated patients may show spontaneous improvement, almitrine-raubasine should accelerate patients' functional rehabilitation.
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PMID:Stroke and functional rehabilitation: the Chinese experience. 951 72

A rat model of ischemic tolerance is useful for studying the intrinsic cellular mechanism of resistance to cerebral ischemia. Many types of preconditioning in the brain have been reported to induce ischemic tolerance; however, evaluation of their neuroprotective effect is primarily limited to differences in counts of surviving cells. A lesser but still large number of neurons die in the neocortex after global ischemia following ischemic tolerance. This study addressed the issue of whether any type of preconditioning could elicit a tolerance that limited the size of cerebral infarct against temporary focal ischemia. Cortical spreading depression was induced for a prolonged period and, after various intervals, the stress of temporary focal ischemia was evaluated in rats. Ten groups of male rats (n=8 each) were studied. In the first group, temporary focal ischemia was induced by occlusion of three vessels (bilateral carotid arteries and left middle cerebral artery, MCA) for 2 h (control). In the second to seventh groups, cortical spreading depression was generated by continuously infusing 4 M potassium chloride (KCl)(1.0 microliter l/h for 2 days) into the left neocortex via an osmotic pump. On days 6, 9, 12, 15, 21 and 24 (day 0=day of pump removal), temporary focal ischemia was induced in one of these groups. In the other three groups, saline was infused instead of KCl, and on day 6, 12 or 21, temporary focal ischemia was induced. All rats were sacrificed 2 days after the ischemia and the infarct volume was analyzed using TTC staining of brain slices. In a separate group of animals, regional cerebral blood flow (rCBF) at the periinfarct area (penumbra) was monitored before and during the ischemia with a laser-Doppler flowmetry (LDF) system on day 12 following saline (n=5) or KCl infusion (n=5) for 48 h. To obtain the absolute rCBF value before ischemia following saline (n=5) or KCl infusion (n=5), hydrogen clearance was examined in the same cortex under the same anesthesia. The cerebral infarct volume was gradually reduced as the interval between the induction of the spreading depression and the induction of temporary focal ischemia was extended. There was a significant reduction in infarct size between the control and the groups in which ischemia was induced on day 12 or 15. There was no significant difference in the preischemic or intraischemic rCBF between the saline and KCl-infused groups. The preconditioning method was demonstrated to limit the size of cerebral infarct after temporary focal cerebral ischemia; tolerance for cerebral infarct developed after an extended interval following a long period of spreading depression.
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PMID:Infarct tolerance against temporary focal ischemia following spreading depression in rat brain. 951 33

Adenosine is a putative neuroprotectant in ischemia, but its role after traumatic brain injury (TBI) is not clear. Metabolites of adenosine, particularly inosine and hypoxanthine, are markers of ischemia and energy failure. Adenosine triphosphate (ATP) breakdown early after injury and metabolism of cyclic adenosine monophosphate (cAMP) are potential sources of adenosine. Further delineation of the magnitude, location, time course, and source of production of adenosine after TBI is needed. We measured adenosine, inosine, and hypoxanthine in brain interstitial fluid after controlled cortical impact (CCI) in the rat. Rats (n = 15) were prepared for TBI induced by CCI. A microdialysis probe was placed in the cortex, and samples were collected every 10 min. After 3 h of equilibration, the catheter was removed, CCI was performed (4 m/sec, depth 2.5 mm), and the catheter was replaced. In the shams, the catheter was removed and replaced without CCI. The injury group included rats (n = 10) subjected to CCI. Within the injury group, the microdialysis probe was placed in the center of the eventual contusion (center, n = 5) or in the penumbral region (penumbra, n = 5). Purine metabolites were measured using ultraviolet-based high-pressure liquid chromatography. Adenosine, inosine, and hypoxanthine were dramatically increased after injury (61-fold, 37-fold, and 16-fold, respectively sham, all p < 0.05, two-way analysis of variance for repeated measures). No changes in cAMP were observed (p = 0.62 vs. sham). Adenosine peaked in the first 20 min and returned to near baseline 40 min, whereas inosine and hypoxanthine peaked at 30 min and remained increased for 40 min after CCI. Interstitial brain adenosine, inosine, and hypoxanthine were increased early after CCI in rats in the contusion and penumbra. ATP breakdown is a potential source of adenosine in this early period while metabolism of cAMP does not appear to play a role. Confirmation of these data in humans may suggest new strategies targeting this important metabolic pathway.
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PMID:Interstitial adenosine, inosine, and hypoxanthine are increased after experimental traumatic brain injury in the rat. 952 16

The purpose of this manuscript is to briefly review the pathophysiology of cerebral ischemia. Ischemic thresholds are well-defined in lower animals. The concept of the ischemic penumbra may include regions of brain around deeper regions of ischemia but has also been defined in terms of brain salvageable by reperfusion or by pharmacological therapies. The principal pathophysiological processes in cerebral ischemia are energy failure, loss of cell ion homeostasis, acidosis, increased intracellular calcium, excitotoxicity, and free radical-mediated toxicity. The underlying biochemical processes are similar regardless of the amount of brain that is made ischemic or the duration of ischemia. The relative contributions of each process are believed to vary significantly especially in relation to the level of cerebral blood flow. Neurons may die by necrosis or apoptosis. In the core of an infarct where blood flow is very low, the predominant process is energy failure and rapid necrotic cell death. Reperfusion of ischemic tissue produces an influx of inflammatory cells and of oxygen that can cause increases in oxygen-derived free radicals. Free radicals are also important in prolonged ischemia. There is interest in changes in gene expression after ischemia. Induction of heat shock proteins suggests that gene expression changes may protect neurons from death. Changes in gene expression also may initiate apoptosis or other detrimental processes. Although advances have been made, there are still no proven pharmacological therapies to rescue ischemic human neurons. Such therapies do appear to be on the horizon.
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PMID:Pathophysiology of cerebral ischemia. 954 Mar 26

The effect of neuroprotective drugs on the early and late electrophysiological manifestations of photothrombotic occlusion of distal branches of middle cerebral artery was studied in rats treated with MK-801 and Cerebrolysin (CL). DC potentials were recorded from the irradiated cortex (ischemic core), from the adjacent penumbra zone and from remote intact cortex. Irradiation elicited after a few minutes of spontaneous spreading depression (SD) waves followed during 10-15 min by focal ischemic depolarization (FID) developing in the irradiated cortex and spreading into the perifocal areas. While the core FID amplitude reached about 30 mV and decayed during subsequent 2 h to 10-13 mV, FID in the penumbra zone was broken by periods of partial repolarization and returned during 30-90 min almost to baseline. At the same time, generation of spontaneous SD waves almost stopped. MK-801 (0.5 mg/kg, i.p., 45 min after ischemia) blocked SD waves, but did not shorten penumbra FID, the decay of which was slowed down to the rate found in the ischemic core. CL treatment (2.5 ml/kg, i.p. , 1 h after ischemia) did not influence FID in the acute phase of the experiment, but its 10-day administration facilitated post-ischemic recovery indicated by higher amplitude of evoked SD waves penetrating into the former penumbra zone. Morphological examination showed that the volume of total and partial necrosis was increased in the MK-801 group and marginally reduced in the CL group. It is suggested that the absence of the SD-induced hyperperfusion episodes in MK-801-treated rats may accelerate perifocal thrombotization in this model of focal ischemia.
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PMID:The effect of MK-801 and of brain-derived polypeptides on the development of ischemic lesion induced by photothrombotic occlusion of the distal middle cerebral artery in rats. 955 70

Oxygenation is the most critical function of blood flow and a sudden reduction in oxygen availability is an inevitable consequence of severe ischemia. The resulting cascade of events may result in the failure of membrane integrity of some cells and necrosis, but in the surrounding zone of tissue, less affected by hypoxia, cells survive to form the ischemic penumbra. The timing of these events is uncertain, but sufficient oxygen is available to these cells to maintain membrane ion pump mechanisms, but not enough for them to generate action potentials and therefore function as neurons. The existence of such areas has been suspected for some time based upon the nature of clinical recovery, but has now been demonstrated by SPECT imaging with a high plasma oxygen concentration under hyperbaric conditions as a tracer. A course of hyperbaric oxygen therapy frequently results in a permanent improvement in both flow and metabolism. These changes apparently represent a reversal of the changes that render neurones dormant and the activity of cells, previously undetectable by standard electrophysiological methods, can now be demonstrated. Three patients are presented in whom recoverable brain tissue has been identified using SPECT imaging and increased cerebral oxygenation under hyperbaric conditions. Improved perfusion from reoxygenation has correlated with clinical evidence of benefit especially with continued therapy.
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PMID:Cerebral oxygenation and the recoverable brain. 958 21

The heterogeneity of c-fos and hsp72 mRNA expression during focal ischemia was studied in mice by combining in situ hybridization with metabolic imaging. Focal ischemia was produced by middle cerebral artery occlusion for 3 h. The infarct core and the penumbra were differentiated by regional ATP and cerebral protein synthesis (CPS) imaging. hsp72 mRNA expression was restricted to the ischemic penumbra, as defined by the dissociation between preserved ATP and suppressed CPS. c-fos mRNA was expressed not only in the penumbra but also in the peri-ischemic normal brain tissue in which both ATP and CPS were preserved. These data demonstrate a highly selective differential expression of immediate-early and stress-related genes in the peri-infarct surrounding which is explained by different mechanisms of gene induction.
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PMID:Differential expression of c-fos and hsp72 mRNA in focal cerebral ischemia of mice. 959 42

The present experiments were undertaken to define changes in tissue calcium metabolism in focal and perifocal ("penumbral") tissues following 2 h of transient middle cerebral artery occlusion (MCAO) in rats, induced with an intraluminal filament occlusion technique. The extracellular calcium concentration ([Ca2+]e) was measured with ion-selective microelectrodes in neocortical focus and penumbra. For measurement of total tissue calcium content, tissue samples from these areas were collected and analyzed with atomic absorption spectrometry. During MCAO, [Ca2+]e in a neocortical focal area fell from a normal value of about 1.2 mM to values around 0.1 mM, suggesting translocation of virtually all extracellular calcium to intracellular fluids. Recirculation was accompanied by re-extrusion of calcium within 5-7 min; however, [Ca2+]e never returned to normal but stabilized at about 50% of the control value for the first 6 h, and decreased further after 24 h. In penumbral areas, [Ca2+]e showed the expected transient decreases associated with spreading depression-like (or ischemic) depolarization waves. Recirculation was followed by return of [Ca2+]e towards normal values. In the focus, water content increased from about 79% to about 80.4% at the end of the 2-h period of ischemia. After 2 h and 4 h of recirculation, the edema was aggravated (mean values 81.9% and 81.2%, respectively). After 6 h and 24 h, the edema was more pronounced (83.6% and 83.8%, respectively). In the penumbra, no significant edema was observed until 6 h and 24 h of recirculation. The total tissue calcium content in the focus (expressed by unit dry weight) increased at the end of the ischemia period demonstrating calcium translocation from blood to tissue. After 6 h and 24 h, the content increased two- to threefold, compared with control. Changes in the penumbra were qualitatively similar but less pronounced, and a significant increase was not observed until after 6 h of recirculation. The results suggest that 2 h of MCAO leads to a profound perturbation of cell calcium metabolism. In focal areas, cells fail to extrude the calcium that is gradually accumulated during reperfusion and show massive calcium overload after the first 4-6 h of recirculation. Penumbral tissues show a similar increase in calcium concentration after 6 h of recirculation.
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PMID:Calcium metabolism of focal and penumbral tissues in rats subjected to transient middle cerebral artery occlusion. 965 36


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