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

The morphological and histochemical changes in the rat brain, resulting from global cerebral ischemia due to cardiac arrest and cessation of respiratory function, connected with the disturbances of blood-brain barrier mechanisms inclined us to perform a series of studies on the localization of specific sugar residues in the membrane glycoprotein chains, using lectin techniques. Chosen lectins, represented by synthetic plant glycoproteins which are specifically bound to particular sugar residues located on the cell surfaces, made it possible to localize the following sugar residues: beta-D-galactose (using Ricinus communis agg.-RCA-1); beta-D-galactosyl (Ricinus communis agglutinin <RCA-1>), N-acetyl-glucosaminyl and N-acetyl-neuraminic acid (Wheat germ agglutinin WGA), N-acetyl-glucosaminyl (Helix pomatia agglutinin <HPA> and Dolichos biflorus agglutinin<DB A>), N-acetyl and N-glycol-neuraminic acid (Limax flavus agglutinin <LFA>), alpha-D-galactosyl and D-galactosyl neuraminic acid (Peanut agglutinin <PNA>), alpha-D-galactosyl and alpha-D-mannosyl (Concanavalin A <Con A>), alpha-D-galactosyl and alpha-D-galactopyranoside (Bandeirea simplicifolia agglutinin A <BSA>). In the presented paper changes in the localization of examined glycoconjugates found both in the vascular network as well as in other morphological elements of the brain (neurons, glial cells and neuropil), resulting from 10 min cardiac arrest, connected with global cerebral ischemia are characterized. In the group of control animals the strongest reaction of the vessels was obtained with RCA-1 and BSA, weaker with WGA and the weakest with DBA and LFA. Experimental rats, examined at different time following resuscitation showed significant changes in the histochemical reaction with use of different lectins. Sugar residues revealed by BSA disappeared from the brain vessels already 3 h following clinical death reappearing at 3 and 14 days after ischemia and regaining the picture described in control animals one year later. Additionally the experimental animals were characterized by a remarkably weaker reaction with WGA while location and intensity of RCA-1 receptors in the brain blood vessels remained unchanged or even increased. Additionally in the group of rats which survived 3 days after ischemia, the number of vascular receptors revealed by DBA also increased. The neuropil was characterized by a strong affinity to the sugar residues recognized by DBA, HPA, BSA, PNA, and LFA. As a rule it was stronger in the white structures of the brain than in the gray ones. Starting from the 24 h of postresuscitation till the end of the observation (1 year) staining reaction of neuropil with the above mentioned lectins was reduced. From the group of glycoconjugates used the strongest reaction in parenchymal brain cellular elements concerned those sugar residues which are identified Con A and HPA. In a group of experimental animals staining reaction with Con A was decreased whereas that with HPA was remarkably increased in all animals which survived ischemia. Additionally, BSA-recognized residues not detectable in normal conditions appeared in the neurons and glial cells of hippocampus and subiculum. The presented results indicate deep histochemical and probably functional changes taking place in endothelial cells as well as in other cellular elements of the brain and in neuropil of animals which survived clinical death. The abnormalities appearing in the early postischemic stage persisted for the long observation time indicating an active and progressing process leading to postischemic encephalopathy.
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PMID:Lectin histochemistry in the rats brain in experimental postresuscitation syndrome. (Early and late changes). 879 96

Rats and gerbils have been used widely to investigate the molecular mechanism of selective neuronal death following transient global ischemia. Recently, the availability of transgenic mice has enabled us to examine the involvement of specific gene products in various pathophysiological conditions. However, there has been only limited information about the experimental model of cerebral ischemia in mice, particularly in regard to selective neuronal death. We examined whether bilateral carotid occlusion produced global forebrain ischemia in seven common mouse strains including C57BL/6, ICR, BALB/c, C3H, CBA, ddY and DBA/2, based on neurological signs, histological findings and cortical microcirculatory as well as India ink perfusion patterns. The C57BL/6 strain was found to be the most susceptible among seven strains. All C57BL/6 mice died within 6 h after permanent bilateral carotid occlusion. After transient bilateral carotid occlusion for 20 min, more than 90% of C57BL/6 mice showed typical neurological signs such as torsion of the neck and rolling fits, and developed selective neuronal death in the hippocampus and caudoputamen. Hypothermia prevented the neuronal death. Visualization of brain vasculature by India ink perfusion indicated that the susceptibility of the mice after bilateral carotid occlusion depended mainly on the degree of anastomosis between carotid and basilar arteries. Our results showed the feasibility of investigating selective neuronal death in transgenic mice with simple temporary occlusion of both common carotid arteries, when those from the C57BL/6 strain or inbred transgenic mice from other strains with the C57BL/6 strain in a back-cross manner are used.
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PMID:C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: selective neuronal death in the murine transient forebrain ischemia. 910 59

The compound 5-(4-chlorophenyl)-2,4-dihydro-4-ethyl-3H-1,2,4-triazol-3-one (MDL 27,192) was evaluated in a variety of rodent models to assess its anticonvulsant profile and its potential neuroprotective activity. MDL 27,192 demonstrated anticonvulsant activity in a wide range of epilepsy models that are genetically-based (audiogenic seizures in the seizure susceptible DBA/2J or Frings mouse; spike wave seizures in genetic absence epilepsy rats of Strasbourg (GAERS), electrically-based (MES seizures in mice and rats, corneally-kindled seizures in rats) and chemically-based (bicuculline, PTZ, picrotoxin, 3-mercaptopropionic acid, quinolinic acid and strychnine). When compared to valproate, orally administered MDL 27,192 was 17-48-fold more potent as an anticonvulsant and showed a safety index one to three-fold greater. Following a timed intravenous administration of PTZ to mice, MDL 27,192, but not phenytoin or carbamazepine, consistently increased the latencies to first twitch and clonus. MDL 27,192 was active in a genetic model of absence epilepsy, the GAERS rat model. These data indicate that MDL 27,192 likely exerts its anticonvulsant action by affecting seizure spread and by raising seizure threshold. MDL 27,192 did not display any signs of tolerance following subchronic (15 day) administration. In tests of neuroprotective potential, MDL 27,192 reduced infarct volume in a permanent middle cerebral artery occlusion model of focal cerebral ischemia in rats and reduced the loss of hippocampal dentate hilar neurons in an animal model of unilateral head injury. In summary, MDL 27,192 possesses a broad-spectrum anticonvulsant profile. The potential for reduced tolerance and neuroprotective activity are additional positive features of MDL 27,192's preclinical profile.
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PMID:Preclinical characterization of MDL 27,192 as a potential broad spectrum anticonvulsant agent with neuroprotective properties. 916 90

Cerebral ischemia models using mice have drawn increasing attention, particularly because of the availability of transgenic animals. However, the variability of intracranial vasculature at the circle of Willis in mice can influence the degree of ischemia in both the bilateral common carotid artery (CCA) occlusion and intraluminal suture occlusion models. We have developed a method to predict the extent of the anastomosis between carotid and vertebrobasilar circulation in three mouse strains (C57BL/6, CBA, and DBA/2) by measuring cortical microperfusion with laser Doppler flowmetry during a 1-minute occlusion of both CCA. When animals showed residual cortical microperfusion of less than 12% during bilateral CCA occlusion, the mice showed absence of functional anastomosis, developed ATP depletion in the frontal cortex during occlusion, and had ischemic neuronal death in the hippocampus and caudoputamen after occlusion for 15 minutes and recirculation for 7 days. Furthermore, those mice exhibited decreased local cerebral blood flow and associated ischemic neuronal death in the hippocampus, within the territory supplied by the posterior cerebral artery, with the intraluminal suture occlusion model. The current study demonstrates the need for assessment of intracranial vasculature in each animal by measuring cortical microperfusion during temporary occlusion of both CCA, no matter whether cerebral ischemia is produced by bilateral CCA occlusion or intraluminal suture occlusion in transgenic mice.
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PMID:Cerebral ischemia after bilateral carotid artery occlusion and intraluminal suture occlusion in mice: evaluation of the patency of the posterior communicating artery. 959 49

It is known that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in both the primary and the secondary prevention of ischemic heart disease. Increasing evidence indicates that statins have protective effects in several neurological diseases including stroke, cerebral ischemia, Parkinson disease, multiple sclerosis, traumatic brain injury and epilepsy. The aim of the present research was to evaluate the effects of some HMG-CoA reductase inhibitors (i.e. lovastatin, simvastatin, atorvastatin, fluvastatin and pravastatin) commonly used for the treatment of hypercholesterolemia in the DBA/2 mice, an animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; i.e. carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive pharmacological interactions. Simvastatin only was active against both the tonic and clonic phase of audiogenic seizures, whereas the other statins tested were only partially effective against the tonic phase with the following order of potency: lovastatin>fluvastatin>atorvastatin; pravastatin was completely ineffective up to the dose of 150mg/kg. The co-administration of ineffective doses of all statins with AEDs generally increased the potency of the latter reducing their ED50 values. In particular, simvastatin was the most active in potentiating the activity of AEDs and the combinations of statins with carbamazepine, diazepam, felbamate, lamotrigine, topiramate and valproate were the most favorable, whereas, the co-administrations with the other AEDs studied was in most cases neutral. The increase in potency was generally associated with an enhancement of motor impairment (TD50); however, the therapeutic index (TD50/ED50) of combined treatment of AEDs with statins was predominantly more favorable than control. Statins administration did not significantly affect the total plasma but, in some cases, it increased the free plasma levels and the brain concentrations of some of the AEDs studied (i.e. carbamazepine, diazepam, phenytoin and valproate); however, these alterations where not statistically significant. Therefore, with the exception of the latter compounds, we might exclude pharmacokinetic interactions and conclude that for the most of AEDs, potentiation was of pharmacodynamic nature. In conclusion, simvastatin, fluvastatin, lovastatin and atorvastatin showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, diazepam, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations. The present results suggest that statins, besides the beneficial cardiovascular effects, might be able to affect brain areas, which might participate in the regulation of seizure susceptibility.
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PMID:Pharmacodynamic potentiation of antiepileptic drugs' effects by some HMG-CoA reductase inhibitors against audiogenic seizures in DBA/2 mice. 2325 28