Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical use of profound hypothermia and total circulatory arrest has been accompanied by occasional postoperative neurological abnormalities. In a series of infant baboons, surface cooling to 32 degrees C (brain) followed by perfusion cooling by cardiopulmonary bypass with a membrane oxygenator and heat exchanger to 18 degrees C was carried out, after which the circulation was stopped for 30 minutes. The animal was rewarmed to 35 degrees C. Marked alterations in the regional cerebral circulation were observed during perfusion cooling and rewarming. Regional cerebral ischemia was negatively correlated with jugular outflow (total cerebral blood flow) during rewarming, while regional hyperemia showed positive correlation both following perfusion cooling and after rewarming. A higher degree of ischemia in brain ischemic samples was found during rewarming than during cooling. These alterations in regional cerebral perfusion were associated with lactacidosis and hyperglycemia after rewarming, and may be considered potentially responsible for posthypothermic cerebral dysfunction.
 ...
PMID:Cerebral effects of profound hypothermia (18 degrees C) and circulatory arrest. 115 33

The effects of dazoxiben, a TXA2 synthetase inhibitor, and indomethacin were compared on cerebrovascular resistance (CVR) and levels of serum TXB2, 6-keto-PGF1 alpha (the stable metabolites of TXA2 and PGI2, respectively) and on protection from acute brain ischaemia caused by ia arachidonic acid (AA) in rabbits. The flow represented the cerebral blood flow (CBF) in two internal jugular arteries were measured with electromagnetic flow meter after occlusion of bilateral vertebral arteries and external jugular arteries. CVR was represented as blood pressure/(CBF.100 g brain). Serum TXB2 and 6-keto-PGF1 alpha levels were determined by radioimmunoassay. The results showed that CVR and BP, EEG, ECG were not affected by treatment with iv dazoxiben 2 or 10 mg/kg. The CVR was enhanced by 35.5 and 49.8% at 30 and 40 min, respectively after iv indomethacin 10 mg/kg. The serum TXB2 level (872 +/- 85) was inhibited to 511 +/- 169 pg/ml (n = 5, P less than 0.05) and 6-keto-PGF1 alpha increased from 668 +/- 309 to 890 +/- 357 pg/ml (n = 5, P less than 0.05) at 30 min after iv 2 mg/kg dazoxiben. However, both TXB2 and 6-keto-PGF1 alpha decreased by 26.4 and 32.7%, respectively at 40 min after iv indomethacin 10 mg/kg. In a model of cerebral ischaemia caused by ia AA in rabbits, the EEG change and enhancement of CVR were antagonized by iv dazoxiben 10 mg/kg completely, but only partly antagonized by indomethacin 10 mg/kg. The results suggest that PGI2 and TXA2 may play a minor role in the regulation of CVR in the physiological condition.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Effect of dazoxiben on cerebrovascular resistance in rabbits]. 262 20

Although cerebral infarction is a destructive process of nerve cells and brain tissue, the nature is not exclusively disintegrating but also includes active cellular reaction which may modify the progression of tissue damage. Most prominent cellular reaction in the area surrounding infarction can be recognized as a trophic or proliferative change of glial cells. In the present study we produced a focal cerebral ischemia in Mongolian gerbils and investigated the dynamic change of astrocytes in the brain adjacent to thalamic infarction. Using immunohistochemical methods, astrocytes were identified with the antibody to astroprotein (GFAP) and the DNA synthesizing (S phase) cells were detected with the antibody to bromodeoxyuridine (BrdU). The posterior communicating artery of a gerbil was occluded by coagulation through the trans-tympanic bulla approach under general anesthesia with ketamine hydrochloride (80 mg/kg, i.p.). Thirty min after intravenous administration of BrdU (200 mg/kg), animals were sacrificed by transcardiac perfusion with 75% ethanol on days 1, 2, 3, 5 and 7 post-infarction. Ethanol-fixed, paraffin-embedded blocks were cut coronally into 6 microns-thick sections at the level of dorsal hippocampus. Double-labeled immunohistochemical technique (avidin biotin peroxidase-complex method) was carried out with each antibody using 3,3'-diaminobenzidine tetrahydrochloride and 4-chloro-1-naphthol as chromogens. The population of GFAP-positive cells and their S-phase fraction (the number of BrdU-positive nuclei divided by the number of GFAP-positive cells expressed in per cent, %) were examined. The data demonstrated that the regional GFAP-positive cells increased continuously between days 1 to 5 (105.9 to 528.8 cells/mm2) postinfarction (44.6 cells/mm2 in normal brain).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Astrocytic proliferation in the brain adjacent to infarcted lesion: immunohistochemical study of astroprotein (GFAP) and bromodeoxyuridine (BrdU)]. 276

The present study was designed to determine the extent to which the brain stem neural networks, normally capable of synchronizing the sympathetic nerve discharge (SND) into 2- to 6- and 10-Hz rhythmic fluctuations, contribute to the control of autonomic reactions during brain hypoxia and/or hypercapnia. Vertebral, cardiac, and renal nerve discharges were recorded electrophysiologically in 34 anesthetized, curarized, and artificially ventilated cats. The sympathetic nerve responses to cerebral ischemia (elicited by reducing the blood supply to the brain), intracranial pressure elevation (Cushing reaction), and systemic asphyxia were tested with special focus on the rhythmic structure of the SND. It has been found that there are two phases of SND changes during cerebral ischemia differing mainly in the frequency content of the signals and less in the compound action potential amplitude. During the first phase the rhythmic generators controlling the tonic sympathetic outflow are more strongly activated, which is reflected in a stronger, more regular, and more widespread manifestation of these rhythms on the efferent neurograms. After some time the normal SND structure abruptly changes to a desynchronized activity with loss of the three main sympathetic rhythms and responsiveness to baroreceptor reflex activation. The same stereotyped changes can be observed regardless of the way in which the brain hypoxia and/or hypercapnia has been produced. Nor does the denervation of peripheral baro- and chemoreceptors substantially alter the general pattern of the responses.
 ...
PMID:Two-phase change of sympathetic rhythms in brain ischemia, Cushing reaction, and asphyxia. 291 4

Recent studies on proton NMR imaging revealed its remarkable sensitivity for detecting cerebral ischemia. Since proton NMR reflects the distribution and state of water in the brain, an NMR imager becomes a sensitive in vivo detector of brain edema developing soon after the energy state is compromized by ischemia. To further clarify the usefulness of NMR imaging to characterize the ischemia-induced changes, correlations between T1 and T2 relaxation times and water content of the normal and ischemic rat and gerbil brain were studied by means of both spectroscopic and in vivo imaging methods. In the spectroscopic experiment on excised rat brain (cortex, white matter, hippocampus and thalamus for normal and ischemia-laden brain), T1 and T2 relaxation times and water content were determined. The ischemic insult was induced for 60 min by the method of Pulsinelli followed by 60 min of reperfusion. All of the T1, T2 and water content significantly increased in the ischemic tissue. Gray-white difference was evident in T1 and T1 was linearly correlated with the water content of the tissue. T2 was by far prolonged in the ischemic tissue compared with the increase in the water content, showing greater sensitivity of T2 for detection of ischemia. In the imaging experiment, coronal NMR imaging at 0.5 tesla was performed employing proton density-weighted saturation recovery (TR = 1.6 s, TE = 14 ms), T1-weighted inversion recovery (TR = 1.6 s, TI = 300 ms, TE = 14 ms) and T2-weighted spin echo (TR = 1.6 s, TE = 106 ms) pulse sequences.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Magnetic resonance imaging of experimental cerebral ischemia: correlations between NMR parameters and water content]. 370 79

During the last decade, a multitude of experimental arguments have led to the concept that EDRF is nitric oxide (NO), a messenger not only involved in the control of vasomotor tone but also in vascular homeostasis, neuronal and immunological functions. Regardless of its origin, endogenous NO is produced through the conversion of L-arginine to L-citrulline by NO-synthase (NOS) from which several isoforms have recently been isolated, purified and cloned. NOS-type I (isolated from brain) and type III (isolated from endothelial cells) are termed "constitutive-NOS" and produce picomolar levels of NO from which only a small fraction elicits physiological responses. These isoforms are regulated by Ca(2+)-calmodulin with NADPH, FAD/FMN and tetrahydrobiopterin as co-factors and reveal a high degree of homology with the amino-acid sequence of cytochrome P450 reductase within the C-terminal domain. Functionally, neuronal-NOS type I is important in neurotransmission (modulation of NMDA receptor), the central control of vascular homeostasis and possibly learning and memory. In the peripheral nervous system, NOS appears to be linked to nonadrenergic noncholinergic (NANC) neuronal pathways. Endothelial-NOS type III is essential for the control of vascular tone in response to the release of endogenous mediators, although shear stress is the major trigger of endothelial-NOS activity under physiological conditions. NOS-type III also contributes to the prevention of abnormal platelet aggregation. NOS-types II and IV (isolated from macrophages) are Ca(2+)-calmodulin independent and are termed "inducible-NOS" since their activation is only promoted under pathophysiological situations where macrophages exert cytotoxic effects in response to cytokines. In contrast with NOS-types I and III, activation of NOS-type II in these cells induces the formation of nanomolar levels of NO which act as a defense mechanism of the immune system. Dysfunctions of the L-arginine-NO pathway have been characterized in multiple diseases (atherosclerosis, hypertension, diabetes, sepsis, cerebral ischemia, etc) and the design of more selective activators/inhibitors of NOS isoforms is a new challenge for the understanding of their pathophysiology and treatment.
 ...
PMID:Nitric oxide: an ubiquitous messenger. 829 80

As the most abundant cell type in the central nervous system, astrocytes are positioned to nurture and sustain neurons, especially in response to cellular stresses, which occur in ischemic cerebrovascular disease. In a previous study (Hori, O., Matsumoto, M., Kuwabara, K., Maeda, M., Ueda, H., Ohtsuki, T., Kinoshita, T., Ogawa, S., Kamada, T., and Stern, D. (1996) J. Neurochem., in press), we identified five polypeptide bands on SDS-polyacrylamide gel electrophoresis, corresponding to molecular masses of about 28, 33, 78, 94, and 150 kDa, whose expression was induced/enhanced in astrocytes exposed to hypoxia or hypoxia followed by replacement into the ambient atmosphere (reoxygenation). In the current study, the approximately 150-kDa polypeptide has been characterized. Chromatography of lysates from cultured rat astrocytes on fast protein liquid chromatography Mono Q followed by preparative SDS-polyacrylamide gel electrophoresis led to isolation of a approximately 150-kDa band only observed in hypoxic cells and which had a unique N-terminal sequence of 15 amino acids. Antisera raised to either the purified approximately 150-kDa band in polyacrylamide gels or to a synthetic peptide comprising the N-terminal sequence detected the same polypeptide in extracts of cultured rat astrocytes exposed to hypoxia; expression was not observed in normoxia but was induced by hypoxia within 24 h, augmented further during early reoxygenation, and thereafter decreased to the base line by 24 h in normoxia. ORP150 expression in hypoxic astrocytes resulted from de novo protein synthesis, as shown by inhibition in the presence of cycloheximide. In contrast to hypoxia-mediated induction of the approximately 150-kDa polypeptide, neither heat shock nor a range of other stimuli, including hydrogen peroxide, cobalt chloride, 2-deoxyglucose, or tunicamycin, led to its expression, suggesting selectivity for production of ORP150 in response to oxygen deprivation, i.e. it was an oxygen-regulated protein (ORP150). Northern and nuclear run-off analysis confirmed the apparent selectivity for ORP150 mRNA induction in hypoxia. Subcellular localization studies showed ORP150 to be present intracellularly within endoplasmic reticulum and only in hypoxic astrocytes, not cultured microglia, endothelial cells, or neurons subject to hypoxia. Consistent with these in vitro results, induction of cerebral ischemia in mice resulted in expression of ORP150 (the latter was not observed in normoxic brain). These data suggest that astroglia respond to oxygen deprivation by redirection of protein synthesis with the appearance of a novel stress protein, ORP150. This polypeptide, selectively expressed by astrocytes, may contribute to their adaptive response to ischemic stress, thereby ultimately contributing to enhanced survival of neurons.
 ...
PMID:Purification and characterization of a novel stress protein, the 150-kDa oxygen-regulated protein (ORP150), from cultured rat astrocytes and its expression in ischemic mouse brain. 861 79

Polyamines and N-methyl-D-aspartate (NMDA) receptors are both thought to play an important role in secondary neuronal injury after cerebral ischemia. Ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, was studied after transient focal cerebral ischemia occurred. Spontaneously hypertensive male rats, each weighing between 250 and 350 g, underwent 3 hours of tandem middle cerebral artery (MCA) and common carotid artery occlusion followed by reperfusion for a period of 3 hours or 21 hours. Intravenous ifenprodil (10 microg/kg/minute) or saline infusion was started immediately after the onset of MCA occlusion and continued throughout the ischemic period. Physiological parameters including blood pressure, blood gas levels, blood glucose, hemoglobin, and rectal and temporal muscle temperatures were monitored. Six rats from each group were evaluated at 6 hours postocclusion for brain water content, an indicator of brain edema, and Evans blue dye extravasation for blood-brain barrier breakdown. Infarct volume was also measured in six rats from each group at 6 and 24 hours postocclusion. Ifenprodil treatment significantly reduced brain edema (82.5 +/- 0.4% vs. 83.5 +/- 0.4%, p < 0.05) and infarct volume (132 +/- 14 mm3 vs. 168 +/- 25 mm3, p < 0.05) compared with saline treatment, with no alterations in temporal muscle (brain) or rectal (body) temperature (35.9 +/- 0.4 degrees C vs. 36.2 +/- 0.2 degrees C; 37.7 +/- 0.4 degrees C vs. 37.6 +/- 0.6 degrees C; not significant). These results demonstrate that ifenprodil has neuroprotective properties after ischemia/reperfusion injury in the absence of hypothermia. This indicates that antagonists selective for the polyamine site of the NMDA receptors may be a viable treatment option and helps to explain some of the pathophysiological mechanisms involved in secondary injury after transient focal cerebral ischemia has occurred.
 ...
PMID:Effects of ifenprodil, a polyamine site NMDA receptor antagonist, on reperfusion injury after transient focal cerebral ischemia. 938 5

Freshly sampled brain tissue exposed to 2,3,5-triphenyltetrazolium chloride (TTC) acquires a red color because mitochondrial enzymes reduce the colorless TTC to a red, water-insoluble formazan deposit. Pan-necrotic areas remain uncolored, which enables quantitation of experimental brain injury by optical scanning and image analysis of serial slices to determine the relative volume of red versus infarcted, non-stained, tissue. The accuracy of this method can be challenged, however, when infarction is accompanied by areas of partial, scattered injury where differences in coloration are difficult to see or quantify. We tested the feasibility of measuring scattered injury using a principle which underlies standard assays for in vitro cell survival, namely extracting deposited formazan with a solvent and measuring its level by spectrophotometry. Anesthetized, adult Sprague Dawley rats were subjected to 12 min of cerebral ischemia to produce selective, delayed neuronal death in hippocampus, striatum and cortex. Some rats also received 6 h of whole-body hypothermia treatment (31.5-32.5 degrees C) immediately after ischemia. Ischemia rats and non-operated controls were sacrificed 1 week later. Hippocampus and portions of cerebrum were incubated 90 min in a 2% TTC solution and then soaked in a measured volume of 50:50 ethanol and dimethylsulfoxide to extract the red formazan product. Spectrophotometric measurements of the extract showed a diminished formazan coloration (absorbance/g brain) in all samples from the untreated ischemia group compared to non-operated controls. This apparent brain injury was attenuated in the group of ischemia rats that received hypothermia treatment. We conclude that solvent extraction and spectrophotometric quantitation of formazan has potential utility as an objective way to index experimental brain injury even if this is diffuse in nature and not amenable to measurement by conventional image analysis techniques.
 ...
PMID:Spectrophotometric measurement of experimental brain injury. 1066 38

Thrombin contributes to edema formation after intracerebral hemorrhage. Recent studies suggest that thrombin may also play a role in ischemic brain damage. In the present study, adult male Sprague-Dawley rats were anesthetized with pentobarbital. Middle cerebral artery (MCA) was occluded using the suture method. We found that brain thrombin activity was elevated after permanent MCA occlusion as was prothrombin messenger RNA expression. Intracerebral injection of a thrombin inhibitor, hirudin, reduced neurological deficits following cerebral ischemia. In contrast, intracerebral administration of exogenous thrombin (at a dose that is non-toxic to normal brain), markedly exacerbated brain edema after transient focal cerebral ischemia. These results indicate that extravascular thrombin inhibition may be a new therapeutic target for cerebral ischemia.
 ...
PMID:Thrombin exacerbates brain edema in focal cerebral ischemia. 1475 26


1 2 Next >>