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

By analyzing histological damages and the regional N-acetylaspartate (NAA) level simultaneously, we evaluated the effect of an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist, YM90K [6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione monohydrochloride], in unilateral forebrain ischemia in gerbils. The right common carotid artery was clipped for 5 min under ether anesthesia, and reperfused for 7 days. The frozen brain sections were lyophilized and the hippocampal CA1 area was dissected out for HPLC assay of NAA. An adjacent section was stained with hematoxylin-eosin for counting survived neurons per 1 mm pyramidal layer of the hippocampal CA1 area. Postischemic administration of YM90K at 20 mg/kg and 25 mg/kg attenuated the decrease of both the number of survived neurons and the NAA level on the ischemic side in a dose-dependent manner. A significant linear correlation was observed between the NAA level and the number of intact neurons. These results indicated that the NAA level could be used as an index of neuroprotective effects of pharmacological agents in global cerebral ischemia.
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PMID:A potent AMPA/kainate receptor antagonist, YM90K, attenuates the loss of N-acetylaspartate in the hippocampal CA1 area after transient unilateral forebrain ischemia in gerbils. 1158 13

Using different models of focal cerebral ischemia, the temporal and spatial rules of metabolism and energy changes in the post-ischemia brain tissue were measured by proton magnetic resonance spectroscopy (1HMRS) to provide valuable information for judging the prognosis of acute focal cerebral ischemia and carrying out effective therapy. Nine healthy Sprague-Dawly rats (both sexes) were randomly divided into two groups: The rats in the group A (n = 4) were occluded with self-thrombus for 1 h; The rats in the group B (n = 5) were occluded with thread-emboli for 1 h. The 1H MRS at 30, 40, 50, 60 min respectively was examined and the metabolic changes of NAA, Cho and Lac in the regions of interest were semiquantitatively analyzed. The spectrum integral calculus area ratio of NAA, Cho, Lac to Pcr + Cr was set as the criterion. The values of NAA.Cho in the regions of interest were declined gradually within 1 h after ischemia, especially, the ratio of Cho/(Pcr + Cr), NAA/(Pcr + Cr) at 60 min had significant difference with that at 50 min (P < 0.05). The ratio of Lac/(Pcr + Cr) began to decrease at 40 min from initial increase of Lac in both A and B groups. MR proton spectrum analysis was a non-invasive, direct and comprehensive tool for the study of cellular metabolism and the status of the biochemical energy in acute ischemia stroke.
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PMID:An experimental proton magnetic resonance spectroscopy analysis on early stage of acute focal cerebral ischemia. 1267 80

Localized proton MR spectroscopy (MRS) was used to quantify cerebral metabolite concentrations in NMRI (n = 8), BALB/c (n = 7), and C57BL/6 (n = 8) mice in vivo and 1 hr after global irreversible ischemia (2.35 T, STEAM, TR/TE/TM = 6000/20/10 ms, 4 x 3 x 4 mm(3) volume, corrections for cerebrospinal fluid). Anatomical MRI and proton MRS revealed significant differences of the C57BL/6 strain in comparison with both BALB/c and NMRI mice. While MRI volumetry yielded larger ventricular spaces of the C57BL/6 strain, proton MRS resulted in elevated concentrations of N-acetylaspartate (tNAA), creatine and phosphocreatine (tCr), choline-containing compounds (Cho), glucose (Glc), and lactate (Lac) relative to BALB/c mice and elevated Glc relative to NMRI mice. Apart from the expected decrease of Glc and increase of Lac 1 hr post mortem, C57BL/6 mice presented with significant reductions of tNAA, tCr, and Cho, whereas these metabolites remained unchanged in BALB/c and NMRI mice. The results support the hypothesis that the more pronounced vulnerability of C57BL/6 mice to brain ischemia is linked to strain-dependent differences of the cerebral energy metabolism.
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PMID:Localized proton MRS of cerebral metabolite profiles in different mouse strains. 1270 64

The authors compared temporal profiles of N-acetylaspartate (NAA) and the NAA/total creatine ratio with neuronal and astrocytic densities and with tissue atrophy in the hippocampal CA1 sector of gerbils after 5-minute bilateral forebrain ischemia and subsequent reperfusion for up to 6 months. The CA1 sector was dissected from 20- micro m lyophilized sections (n = 5) for NAA, phosphocreatine, and creatine assays using high-performance liquid chromatography. Adjacent 10- micro m sections were used for immunohistochemical analysis to follow neuronal and astrocytic responses. The NAA concentration was significantly (P<0.01) decreased after 7 days but leveled off thereafter. The NAA/total creatine (phosphocreatine + creatine) ratio was significantly decreased after 7 days and further decreased (P<0.05) after 6 months. Extensive neuronal damage developed beyond 7 days, while reactive astrogliosis progressed throughout the observation period. There was a good linear correlation (P<0.01) between astroglial density and the NAA/total creatine ratio beyond 7 days. The thickness of the CA1 sector was significantly reduced after 1 month and further reduced after 6 months. Although both NAA level and the NAA/total creatine ratio seemed to be indicators of neuronal damage, the latter could be influenced by reactive astrogliosis with progression of tissue atrophy.
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PMID:N-acetylaspartate to total creatine ratio in the hippocampal CA1 sector after transient cerebral ischemia in gerbils: influence of neuronal elements, reactive gliosis, and tissue atrophy. 1279 18

The NMR relaxation times (T(1rho), T(2), and T(1)) of water, N-acetylaspartate (NAA), creatine (Cr), choline-containing compounds (Cho), and lactate (Lac) were quantified in rat brain at 4.7 T. In control animals, the cerebral T(1rho) figures, as determined with a spin-lock field of 1.0 G, were 575 +/- 30 ms, 380 +/- 19 ms, 705 +/- 53 ms, and 90 +/- 1 ms for NAA, Cr, Cho, and water, respectively. The T(1rho) figures were 62-103% longer than their respective T(2) values determined by a multiecho method. In global (ischemic) ischemia, T(1rho) of NAA declined by 34%, that of Cr and Cho did not change, and that of water increased by 10%. The T(1rho) of lactate in ischemic brain was 367 +/- 44 ms. Similar patterns of changes were observed in the multiecho T(2) of these cerebral metabolites. The T(1) of water and NAA changed in a fashion similar to that of T(1rho) and T(2). These results show differential responses in metabolite and water T(1rho) relaxation times following ischemia, and indicate that metabolite T(1rho) and T(2) relaxation times behave similarly in the ischemic brain. The contributions of dipolar and nondipolar effects on T(1rho) relaxation in vivo are discussed in this work.
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PMID:Quantitative T1rho NMR spectroscopy of rat cerebral metabolites in vivo: effects of global ischemia. 1512 67

We examined the efficacy of the liposoluble iron chelator 2,2'-dipyridyl (DP) in reducing histological damage in rats submitted to cerebral ischemia and the mechanisms involved in the potential cytoprotection. For this purpose, DP (20 mg/kg, i.p.) was administered 15 min before and 1 h after induction of cortical photothrombotic vascular occlusion in rat. Histological studies were performed to assess infarct volume (at days 1 and 3 postischemia) and astromicroglial activation (at day 3 postischemia). Damage to endothelial and neuronal cells was evaluated at day 1 postischemia by quantitative measurements of Evans Blue extravasation and N-acetylaspartate levels, respectively. Cerebral blood flow was recorded in the ischemic core by laser-Doppler flowmetry within the 15 min to 2 h period after photothrombosis. At 4-h postischemia, radical oxygen species (ROS) production was evaluated by measuring brain glutathione concentrations. The cortical expression of the proteins heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1alpha (HIF-1alpha) was analyzed by Western blotting at day 1 postischemia. Infarct volume and ischemic damage to endothelial and neuronal cells were significantly reduced by DP treatment. This cytoprotection was associated with a reduction in ROS production, perfusion deficits, and astrocytic activation. DP treatment also resulted in significant changes in HO-1 (+100%) and HIF-1alpha (-50%) protein expression at the level of the ischemic core. These results report the efficacy of the liposoluble iron chelator DP in reducing histological damage induced by permanent focal ischemia.
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PMID:Cytoprotective efficacy and mechanisms of the liposoluble iron chelator 2,2'-dipyridyl in the rat photothrombotic ischemic stroke model. 1528 Apr 35

The hippocampus is injured in both hypoxia-ischemia (HI) and perinatal iron deficiency that are co-morbidities in infants of diabetic mothers and intrauterine growth restricted infants. We hypothesized that preexisting perinatal iron deficiency predisposes the hippocampus to greater injury when exposed to a relatively mild HI injury. Iron-sufficient and iron-deficient rats (hematocrit 40% lower and brain iron concentration 55% lower) were subjected to unilateral HI injury of 15, 30, or 45 mins (n=12 to 13/HI duration) on postnatal day 14. Sixteen metabolite concentrations were measured from an 11 microL volume on the ipsilateral (HI) and contralateral (control) hippocampi 1 week later using in vivo 1H NMR spectroscopy. The concentrations of creatine, glutamate, myo-inositol, and N-acetylaspartate were lower on the control side in the iron-deficient group (P<0.02, each). Magnetic resonance imaging showed hippocampal injury in the majority of the iron-deficient rats (58% versus 11%, P<0.0001) with worsening severity with increasing durations of HI (P=0.0001). Glucose, glutamate, N-acetylaspartate, and taurine concentrations were decreased and glutamine, lactate and myo-inositol concentrations, and glutamine/glutamate ratio were increased on the HI side in the iron-deficient group (P<0.01, each), mainly in the 30 and 45 mins HI subgroups (P<0.02, each). These neurochemical changes likely reflect the histochemically detected neuronal injury and reactive astrocytosis in the iron-deficient group and suggest that perinatal iron deficiency predisposes the hippocampus to greater injury from exposure to a relatively mild HI insult.
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PMID:Perinatal iron deficiency predisposes the developing rat hippocampus to greater injury from mild to moderate hypoxia-ischemia. 1686 55

Previous studies have found that rats subjected to 15-min transient middle cerebral artery occlusion (MCAO) show neurodegeneration in the dorsolateral striatum only, and the resulting striatal lesion is associated with increased T1-weighted (T1W) signal intensity (SI) and decreased T2-weighted (T2W) SI at 2-8 weeks after the initial ischemia. It has been shown that the delayed increase in T1W SI in the ischemic region is associated with deposition of paramagnetic manganese ions. However, it has been suggested that other mechanisms, such as tissue calcification and lipid accumulation, also contribute to the relaxation time changes. To clarify this issue, we measured changes in relaxation times, lipid accumulation, and elemental distributions in the brain of rats subjected to 15-min MCAO using MRI, in vivo 1H MR spectroscopy (MRS), and synchrotron radiation X-ray fluorescence (SRXRF). The results show that a delayed (2 weeks after ischemia) increase in T1W SI in the ischemic striatum is associated with significant increases in manganese, calcium, and iron, but without evident accumulation of MRS-visible lipids or hydroxyapatite precipitation. It was also found that 15-min MCAO results in acutely reduced N-acetylaspartate (NAA)/creatine (Cr) ratio in the ipsilateral striatum, which recovers to the control level at 2 weeks after ischemia.
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PMID:Delayed changes in T1-weighted signal intensity in a rat model of 15-minute transient focal ischemia studied by magnetic resonance imaging/spectroscopy and synchrotron radiation X-ray fluorescence. 1689 83

The neuroprotective effect of choline succinate was studied in rats with chronic cerebral ischemia induced by ligation of both common carotid arteries. Two approaches were used to evaluate the neuroprotective effect: cognitive ability tests (passive avoidance test and Morris water maze test) and determination of the brain content of N-acetylaspartate, a marker of functional neurons, by 1H NMR spectroscopy in vivo. Choline succinate administration significantly improved memory and learning in ischemic rats and prevented the ischemia-induced decrease in the cerebral level of N-acetylaspartate. Thus, choline succinate demonstrated a neuroprotective effect in conditions of ischemic brain injury.
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PMID:[Neuroprotective effect of choline succinate in rats with experimental chronic cerebral ischemia evaluated by cognitive ability tests]. 1766 62

Conventional ways of monitoring reperfusion in acute ischemic stroke have several limitations. In searching for an alternative, we evaluated biochemical serum markers of stroke change in relation to reperfusion. N-acetylaspartate (NAA) is a small amino acid synthesized by neuronal mitochondria, which can be released in the extracellular space after reperfusion in animal models of brain ischemia. S100B is a well-known peripheral marker of brain damage in various neurologic diseases, including stroke. Serum samples were analyzed from 13 patients with ischemic stroke who were either treated conservatively or with recombinant tissue plasminogen activator. Blood was drawn at baseline; after 30 minutes; after 1, 2, 4, and 8 hours; and between 12 to 24 hours. Serum concentrations of NAA were analyzed using a gas chromatography-mass spectrometry method. S100B was analyzed using an automated immunoluminometric assay. Reperfusion was assessed using transcranial Doppler and clinical criteria. Reperfusion (n = 4) was associated with a transient rapid increase in serum NAA levels. Such an early rapid increase of NAA was not observed for patients with persistent occlusion at 12 to 24 hours (n = 4) and patients with no occlusion on baseline transcranial Doppler (n = 5). NAA peak levels and area under the curve values were significantly higher after reperfusion in comparison with normal transcranial Doppler findings or persistent occlusion (P = .003 and P = .05, respectively). No differences were found between these groups for S100B levels. In patients with acute ischemic stroke, serum NAA levels transiently raise after reperfusion.
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PMID:N-acetylaspartate: serum marker of reperfusion in ischemic stroke. 1790 83


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