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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a randomized double-blind placebo-controlled study in 30 patients with acute ischemic stroke, the effect of the adenosine uptake blocker propentofylline on regional brain glucose metabolism (rCMRglu) was investigated using repeated positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG). Treatment was initiated within 48 h after onset of symptoms. The clinical course was followed for 3 months. In the propentofylline group, after 14 days rCMRglu was increased in the infarct by 37.3% and was practically unchanged in other brain regions, whereas in the control group glucose metabolism had decreased in all regions (1.4-13.4%). These differences were significant between the two groups [Analysis of variance (ANOVA) p = 0.005]. Although there was a trend toward greater clinical improvement in the propentofylline-treated patients, this did not reach statistical significance. The results correspond to experimental data showing that propentofylline improves energy metabolism in cerebral ischemia. A clinical trial is needed to determine whether this new therapeutic principle can be successfully used in acute human stroke.
J Cereb Blood Flow Metab 1993 May
PMID:Effect of propentofylline on regional cerebral glucose metabolism in acute ischemic stroke. 847 10

Perfusion and diffusion-weighted magnetic resonance imaging (MRI) can demonstrate, respectively, cerebral ischemia and ischemic brain injury in the first several hours after onset of symptoms, when proton density and T2-weighted MRI may appear normal. It is hypothesized that these techniques could distinguish regions destined for infarction from those that will not progress to infarction. We provide preliminary evidence from an analysis of 19 patients with severely disabling clinical deficits attributable to ischemia in at least an entire division of the middle cerebral artery, that initial perfusion and diffusion MRI were more accurate than conventional MRI in predicting no, partial or complete improvement--17 of 19 cases (p < 0.0001) versus 10 of 19 cases, respectively. In the subset of patients studied within 6 h of onset, diffusion/perfusion MRI was an even better predictor than conventional MRI--11 of 12 versus four of 12, respectively. In this small sample of patients with severe clinical deficits, perfusion and diffusion MRI were highly accurate in distinguishing those who would improve from those who would not. These results need to be confirmed in a larger prospective study, which may support a future role in the initial screening, selection, and evaluation of patients with stroke for acute pharmacologic interventions.
J Cereb Blood Flow Metab 1996 Jan
PMID:Clinical outcome in ischemic stroke predicted by early diffusion-weighted and perfusion magnetic resonance imaging: a preliminary analysis. 853 May 55

Cerebral infarction initiates a cascade of molecular events, leading to proteolytic cell death. Matrix-degrading metalloproteinases (MMPs) are neutral proteases involved in extracellular matrix damage. Type IV collagenase is an MMP that increases cerebral capillary permeability after intracerebral injection and may be important along with plasminogen activators (PA) in secondary brain edema in stroke. Therefore, we measured MMPs and PAs in spontaneously hypertensive (SHR) or Wistar-Kyoto (WKY) rats with permanent middle cerebral artery occlusion (MCAO). Brain tissue was assayed for MMPs and PAs at 1, 3, 12, and 24 h and 5 days after occlusion, using substrate gel polyacrylamide electrophoresis (zymography). SHR showed an increase in 92-kDa type IV collagenase (gelatinase B) in the infarcted hemisphere compared with the opposite side at 12 and 24 h (p < 0.05). Gelatinase A remained the same in both infarcted and normal tissue until 5 days after injury, when it increased significantly (p < 0.05). Urokinase-type PA was increased significantly at 12 and 24 h and 5 days, while tissue-type PA was decreased significantly at 1, 12, and 24 h in the ischemic compared with the nonischemic hemisphere. Gelatinase B was markedly increased in SHR at 12 and 24 h compared with WKY (p < 0.05). Secondary vasogenic edema is maximal 1-2 days after a stroke, which is the time that gelatinase B was elevated. The time of appearance of gelatinase B suggests a role in secondary tissue damage and vasogenic edema, while gelatinase A may be involved in tissue repair.
J Cereb Blood Flow Metab 1996 May
PMID:Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. 862 40

Stroke trials are initiated after demonstrated pharmacological protection in animal models. NBQX protects CA1 neurons against global ischemia; however, this glutamate antagonist induces a period of subnormal temperature (e.g., a decrease of only 1.0-1.5 degrees C) lasting several days. In this study, NBQX (3 x 30 mg/kg, i.p.) was administered starting 60 min after reperfusion, and brain temperature had declined significantly below vehicle-treated animals by 2 h after reperfusion. When the postischemic brain temperature of NBQX-treated gerbils was regulated, no neuronal protection was found. Mimicking an NBQX-induced temperature profile for 28 h postischemia yielded histological protection 4 days later comparable to that of NBQX. However, both the NBQX and temperature simulation groups showed decreased protection after 10-day survival. Our data suggest that a protracted period of subnormal temperature during postischemic period can obscure the interpretation of preclinical drug studies.
J Cereb Blood Flow Metab 1996 May
PMID:Neuroprotection after several days of mild, drug-induced hypothermia. 862 52

Magnetic resonance water diffusion imaging can detect early ischemic changes in stroke. Using a middle cerebral artery occlusion model, we examined which range of values of the orientation-independent diffusion quantity Dav = 1/3Trace(D) = 1/3(Dxx + Dyy + Dzz) is an early noninvasive indicator of reduced cerebral perfusion and focal brain injury. Cats underwent either a 30-min occlusion followed by 3.5 h reperfusion (n = 7) or a 60-min occlusion followed by 4-h reperfusion (n = 6). Repeated measurements of CBF were made with radiolabeled microspheres, and acute focal injury was measured with triphenyltetrazolium chloride (TTC) staining. During occlusion, the decrease in Dav correlated with CBF for caudate [30-min occlusion (n = 13): p < 0.0001: 60-min occlusion (n = 6): p < 0.02] and for cortex [30-min occlusion (n = 12): p < 0.0001: 60-min occlusion (n = 5): p < 0.04]. Variable caudate and hemispheric injury levels were found among cats in both groups. The area of tissue injury demarcated by TTC began to correlate with the area of reduced Dav by 30 min of occlusion (p < 0.02), and this correlation improved (p < 0.0001) at 1, 1.5, and 2.0 h after the onset of occlusion. The time necessary to reach a one-to-one correspondence between the percent of hemisphere injured and the percent of hemispheric area with Dav < 0.65 x 10(-9) m2/s was 2 h after occlusion. Thus, the absolute value of Dav is a good indicator of the risk of tissue injury, whereas the combination of Dav and the length of time of Dav reduction is an excellent predictor of acute focal tissue injury demarcated by TTC staining.
J Cereb Blood Flow Metab 1996 Sep
PMID:Correlation of the average water diffusion constant with cerebral blood flow and ischemic damage after transient middle cerebral artery occlusion in cats. 878 32

Changes of neuronal excitability and gamma-aminobutyric acid (GABAA)-receptor expression were studied in the surround of photothrombotic infarcts, which were produced in the sensorimotor cortex of the rat by using the rose bengal technique. In a first series of experiments, multiunit recordings were performed on anesthetized animals 2-3 mm lateral from the lesion. Mean discharge frequency was considerably higher in recordings from lesioned animals (> 100 Hz in the first postlesional week) compared with control animals (mean, 15 Hz). These alterations were already present after 1 day but were most pronounced 3 to 7 days after lesion induction. Thereafter the hyperexcitability declined again, although it remained visible up to 4 months. In a second series of experiments, the GABAA-receptor expression was studied autoradiographically. This revealed a reduction of GABAA receptors in widespread brain areas ipsilateral to the lesion. The reduction was most pronounced in the first days after lesion induction and declined with longer intervals. It is concluded that cortical infarction due to photothrombosis leads to a long-lasting and widespread reduction of GABAA-receptor expression in the surround of the lesion, which is associated with an increased neuronal excitability. Such alterations may be responsible for epileptic seizures that can be observed in some patients after stroke and may contribute to neurologic deficits after stroke.
J Cereb Blood Flow Metab 1996 Sep
PMID:Neuronal hyperexcitability and reduction of GABAA-receptor expression in the surround of cerebral photothrombosis. 878 34

We studied the effect of a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate antagonist, YM90K [6-(1H-imidazol-1-yl)-7-nitro-2, 3(1H, 4H)-quinoxalinedione monohydrochloride], in a focal cerebral ischemia model using anesthetized cats. Cats were subjected to permanent occlusion of the middle cerebral artery (MCA) for 6 h, then killed and examined histologically. The amount of ischemic damage was assessed in 12 stereotaxic coronal sections. Treatment with YM90K (i.v. infusion of 0.5 mg/5 ml/kg/h) starting 10 min after MCA occlusion markedly reduced the volume of ischemic damage (from 2823 +/- 164 mm3 of the cerebral hemisphere in saline-treated cats to 1737 +/- 305 mm3 in YM90K-treated cats). No essential differences were observed between YM90K-and saline-treated cats concerning physiological variables or brain temperature. These results further support the notion that the AMPA/kainate receptor plays an important role in the pathogenesis of focal cerebral ischemia. This evidence for the neuroprotective efficacy of YM90K in a gyrencephalic species suggests its therapeutic potential in the treatment of human stroke.
J Cereb Blood Flow Metab 1996 Sep
PMID:Neuroprotective effect of YM90K, a novel AMPA/kainate receptor antagonist, in focal cerebral ischemia in cats. 878 40

Glutamate (Glu) neurotoxicity is an important element of a number of neurological disorders including central nervous system (CNS) ischemia. We evaluated the effects of the novel AMPA Glu antagonist LY293558 on functional neurological outcome in two rabbit stroke models. In the reversible spinal cord ischemia model, ischemia of the caudal lumbar spinal cord was produced by temporary occlusion of the abdominal aorta. LY293558 was administered 5 min after recirculation as a 16 mg/kg i.v. bolus followed by 2.2 mg/kg infused over 1 h. Control animals received saline. LY293558 significantly increased the duration of ischemia required to produce paraplegia, from 30.5 +/- 15.8 min (mean +/- SD) controls to 50.1 +/- 11.5 in treated animals (p < 0.01). In an irreversible model of cerebral ischemia, 50 microns plastic microspheres were injected into the carotid artery and lodged in the cerebral microvasculature. LY293558 did not significantly reduce neurological damage in this model. These data suggest that LY293558 may have therapeutic benefit following some types of ischemic injury.
J Cereb Blood Flow Metab 1996 Sep
PMID:The AMPA antagonist LY293558 improves functional neurological outcome following reversible spinal cord ischemia in rabbits. 878 41

Cortical spreading depression (CSD) has been implicated in the migraine aura and in stroke. This study demonstrates near-infrared spectroscopy (NIRS) for the first time as capable of noninvasive on-line detection of CSD in the pentobarbital-anesthetized rat. CSD was accompanied by a brief and rapid increase of regional CBF (by laser-Doppler flowmetry) to 200-400% baseline. NIRS demonstrates that this hyperperfusion is associated with concentration increases of oxyhemoglobin, while deoxyhemoglobin decreases. Simultaneously, oxygen partial pressure, measured on the brain surface with a solid-state polarographic probe, was shown to be raised by at least 14 mm Hg during CSD. Oxygen-dependent phosphorescence life-time quenching measurements confirmed this finding. NIRS data on cytochrome aa3, however, showed a CSD-related shift toward a more reduced state, despite raised blood oxygenation. This may suggest either limited O2 transport from the blood to mitochondria or decreased oxygen utilization during CSD as supposed by theories about compartmentalization of energy metabolism favoring glycolytic rather than aerobic energy supply during CSD. However, the data on cytochrome aa3 warrant caution and are discussed critically. Nitric oxide synthase inhibition by systemic application of N'-nitro-L-arginine had no significant effect on the perfusion response or the tissue PO2 during CSD. During most CSD episodes, a brief decrease in MABP by 4-8 mm Hg was noted that might be caused by functional decortication during CSD.
J Cereb Blood Flow Metab 1996 Nov
PMID:Systemic nitric oxide synthase inhibition does not affect brain oxygenation during cortical spreading depression in rats: a noninvasive near-infrared spectroscopy and laser-Doppler flowmetry study. 889 81

Studies in humans suggest that regions that show maximal increases in brain oxygen extraction fraction (OEF) in the hours following an ischemic episode are those most vulnerable for infarction and are often, although not always, associated with the final site of infarction. To clarify this issue, we followed the hemodynamic and metabolic characteristics of regions with an initially maximally increased OEF and compared them with the ultimately infarcted region in an experimental stroke model. Positron emission tomography (PET) was used to obtain functional images of the brain prior to and following reversible unilateral middle cerebral artery occlusion (MCAO) in 11 anesthetized baboons. To model early reperfusion, the clips were removed 6 h after occlusion. Successive measurements of regional CBF (rCBF), regional CMRO2 (rCMRO2), regional cerebral blood volume, and regional OEF (rOEF) were performed during the acute (up to 2 days) and chronic (> 15 days) stage. Late magnetic resonance imaging (MRI) scans (co-registered with PET) were obtained to identify infarction. Reversible MCAO produced an MRI-measurable infarction in 6 of 11 baboons; the others had no evidence of ischemic damage. Histological analysis confirmed the results of the MRI investigation but failed to show any evidence of cortical ischemic damage. The lesion was restricted to the head of the caudate nucleus, internal capsule, and putamen. The infarct volume obtained was 0.58 +/- 0.31 cm3. The infarcts were situated in the deep MCA territory, while the area of initially maximally increased OEF was within the cortical mantle. The mean absolute rCBF value in the infarct region of interest (ROI) was not significantly lower than in the highest-OEF ROI until 1-2 days post-MCAO. Cerebral metabolism in the deep MCA territory was always significantly lower than that of the cortical mantle; decreases in CMRO2 in the former region were evident as early as 1 h post-MCAO. In the cortical mantle, the rOEF was initially significantly higher than in the infarct-to-be zone. Subsequently, the OEF declined in both regions. The differences in the time course of changes in CMRO2 and OEF between these two regions, with the eventually infarcted area showing earlier metabolic degradation and in turn decline in OEF, presumably underlie their different final outcomes. In conclusion, following MCAO, the region that shows an early maximal increase in the OEF is both topographically and physiologically distinct from the region with final consolidated infarction if reperfusion is allowed at 6 h. This high OEF, although indicative of a threatened condition, is not an indicator of inescapable consolidated infarction and is thus a situation in which therapy could be envisaged. Whether or not it is at risk of infarction and thus constitutes one target for therapy remains to be seen.
J Cereb Blood Flow Metab 1996 Nov
PMID:Relationships between high oxygen extraction fraction in the acute stage and final infarction in reversible middle cerebral artery occlusion: an investigation in anesthetized baboons with positron emission tomography. 889 90


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