Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over 21,000 hospital episodes due to cerebrovascular disease (CVD, ICD-8 nos. 430-438) were registered in the Helsinki hospitals in 1970-1980. Of those 17,629 were identified as new cases. The age-adjusted incidence of haemorrhagic and thrombotic stroke (430-433) declined during the period 1970-1975 from 221 to 139 cases/100,000 inhabitants, whereafter no further decrease was observed. The decline in incidence was significant in both sexes. Analysis by diagnosis group showed that the decrease was confined to the incidence of haemorrhagic stroke (430-432), whereas the incidence of thromboembolic stroke (433, 434) and transient ischaemic attacks (435) remained virtually unchanged. Survival was mainly determined by patient age and type of CVD. Intracerebral haemorrhage and occlusion of precerebral arteries exhibited the poorest short-term prognosis. About half of the patients hospitalised due to cerebral thrombosis and embolism survived over one year. Long-term prognosis of the major CVD groups was very poor with only 10% of the patients alive after eight years. Transient cerebral ischaemia and subarachnoid haemorrhage had a clearly better prognosis, the survival rates after eight years being 45 and 30%, respectively.
 ...
PMID:The incidence and prognosis of cerebrovascular disease in hospital patients in Helsinki, Finland, in the decade 1970-1980. 359 65

The gerbil model was used to assess the therapeutic effects of the calcium antagonist nimodipine on cerebral ischemia. Transient cerebral ischemia was produced in each gerbil by bilateral common carotid occlusion of 10-, 15- or 20-min duration. Nimodipine (0.01 or 0.1 mg/kg) was administered intraperitoneally just before the carotid occlusion or 10-30 min after the removal of the arterial clips. Morbidity of each animal was evaluated using the stroke index, and the sum of stroke indices was calculated for evaluating the overall morbidity during a particular period of reperfusion. Mortality was observed for 24 hours after clip removal. Although, depending on the timing of the drug administration, the low-dose (0.01 mg/kg) nimodipine worsened the morbidity in the gerbils with 10-min ischemia, the high-dose (0.1 mg/kg) of the drug had a clear beneficial effect on the mortality associated with cerebral ischemia. These results are considered worthwhile for further trials to assess the usefulness of nimodipine as a therapeutic agent in the management of the acute ischemic stroke.
Stroke
PMID:The effect of the calcium antagonist nimodipine on the gerbil model of experimental cerebral ischemia. 373 60

Transient cerebral ischemia and stroke may occur despite previous occlusion of the artery supplying the appropriate part of the brain. After occlusion of the internal carotid artery, emboli may pass from the "stump" of the occluded artery to later produce transient cerebral ischemia or a stroke. Transient cerebral ischemia and stroke are due to a variety of conditions, some of which are strongly correlated with platelet thromboembolism, while others have little primary relation to thrombosis. The impact of this on therapeutic considerations is obvious. Thromboembolism related to myxomatous degeneration of the mitral valve (mitral valve prolapse) is a factor to consider in determining the cause of a stroke in a younger person. The prognosis for the different varieties of threatened stroke is incompletely known. When due to arteriosclerosis of the large cerebral arteries, transient cerebral ischemia and minor strokes pose a cumulative threat for a major stroke or death of 13% in the first year, 22% in the second year and 30% in the third year.
 ...
PMID:Randomized trial of therapy with platelet antiaggregants for threatened stroke. 2: Observations on the pathogenesis and natural history of threatened stroke. 698 64

Transient cerebral ischemia was induced in rabbits by selective infusion of arachidonic acid (0.35 mg/kg in 15 sec) into the internal carotid artery. Platelet emboli caused transient ischemia of the brain, reaching a maximum within a few seconds after injection. After embolism the EEG flattened, blood flow stopped in almost the entire injected hemisphere, cortical pH gradually fell from 7.31 +/- 0.09 to 7.05 +/- 0.10 and cortical K+ activity rose from 4.7 +/- 1.8 to 12.7 +/- 6.4 mmol/kg H2O. Complete ischemia lasted 3-5 min; then cerebral circulation was gradually restored without reactive hyperemia. Forty-five min after embolization, circulation had been resumed in almost the entire injected hemisphere, whereas metabolic changes were still disturbed. Eighty percent of the animals recovered complete neurological function and 20% showed permanent damage confirmed by histological examination after 1 week of recovery.
Stroke
PMID:Platelet embolism in rabbit brain. 730 69

Transient cerebral ischemia (5 min) releases unesterified fatty acids from membrane phospholipids, increasing brain concentrations of fatty acids for up to 1 h following reperfusion. To understand the reported anti-ischemic effect of Ginkgo biloba extract (EGb 761), we monitored its effect on brain fatty acid reincorporation in a gerbil-stroke model. Both common carotid arteries in awake gerbils were occluded for 5 min, followed by 5 min of reperfusion. Animals were infused intravenously with labeled arachidonic (AA) or palmitic acid (Pam), and rates of incorporation of unlabeled fatty acid from the brian acyl-CoA pool were calculated by the model of Robinson et al. (1992), using quantitative autoradiography and biochemical analysis of brain acyl-CoA. Animals were treated for 14 d with 50 or 150 mg/kg/d EGb 761 or vehicle. Ischemia-reperfusion had no effect on the rate of unlabeled Pam incorporation into brain phospholipids from palmitoyl-CoA; this rate also was unaffected by EGb 761. In contrast, ischemia-reperfusion increased the rate of incorporation of unlabeled AA from brain arachidonoyl-CoA by a factor of 2.3-3.3 compared with the control rate; this factor was further augmented to 3.6-5.0 by pretreatment with EGb 761. There is selective reincorporation of AA compared with Pam into brain phospholipids following ischemia. EGb 761 further accelerates AA reincorporation, potentially reducing neurotoxic effects of prolonged exposure of brain to high concentrations of AA and its metabolites.
 ...
PMID:Effects of EGb 761 on fatty acid reincorporation during reperfusion following ischemia in the brain of the awake gerbil. 977 47

Phospholipid degradation is an important promoter of neuronal death after transient cerebral ischemia. Phospholipid hydrolysis by phospholipase A2 (PLA2) after transient cerebral ischemia releases arachidonic acid. Arachidonic acid metabolism results in formation of reactive oxygen species, lipid peroxides, and toxic aldehydes (malondialdehyde, 4-hydroxynonenal, and acrolein). Citicoline (cytidine-5'-diphosphocholine), an intermediate in phosphatidylcholine synthesis, has undergone 13 phase III clinical trials for stroke, and is being evaluated for treatment of Alzheimer's and Parkinson's diseases. Here we examined the effect of citicoline on PLA2 activity in relationship to attenuating hydroxyl radical (OH*) generation and lipid peroxidation after transient forebrain ischemia in gerbil. High Ca2+ dependency (millimolar range) of PLA2 activity suggests that secretory PLA2 is the predominant isoform in membrane and mitochondria. Citicoline attenuated the increase in PLA2 activity in both membrane and mitochondrial fractions. In vitro, citicoline and its components choline and cytidine had no effect on the PLA2 activity. Thus, citicoline is not a "direct PLA2 inhibitor." Citicoline also significantly attenuated loss of cardiolipin and arachidonic acid release from phosphatidylcholine and phosphatidylethanolamine. Transient cerebral ischemia resulted in significant formation of OH* and malondialdehyde, and citicoline significantly attenuated their formation. These results suggest that citicoline provides neuroprotection by attenuating the stimulation of PLA2.
 ...
PMID:Phospholipase A2, hydroxyl radicals, and lipid peroxidation in transient cerebral ischemia. 1458 Mar 22

Disruption of blood-brain barrier (BBB), mediated through matrix metalloproteinases (MMPs), is a critical event during cerebral ischemia. While neuroprotective effects of estrogens have been well established in ischemic stroke models, the effects of estrogens on BBB integrity remain to be elucidated. In the present study, we determined effects of 17beta-estradiol (E2) on BBB disruption induced by transient focal cerebral ischemia and its effects on MMP2 and MMP9 activation. Transient cerebral ischemia was induced by middle cerebral artery (MCA) occlusion for 1 h followed by reperfusion in ovariectomized rats. E2 (100 microg/kg) or vehicle was administered 2 h before MCA occlusion. BBB integrity was determined by fluorescent detection of extravasated Evans blue. In separate experiments, effect of E2 on MMP2 and MMP9 expression and activation was determined by immunoblot and MMPs activity assay. E2 treatment prevented more than 50% and 30% of BBB disruption in the ischemic cortex and subcortex at 4 h after reperfusion, respectively. MMP2 and MMP9 expression was elevated at 2 h and peaked at 4 h after reperfusion in the ischemic cortex, which was markedly reduced by E2 treatment. E2 treatment also attenuated the increase of MMPs activity induced by ischemia-reperfusion injury. In conclusion, estrogens could attenuate BBB disruption induced by transient cerebral ischemia, by inhibition of MMP2 and MMP9 activation. Our results suggest an important role of estrogens as multiple targeting protectants against ischemic stroke on cellular as well as vascular components of central nervous system.
 ...
PMID:17beta-Estradiol attenuates blood-brain barrier disruption induced by cerebral ischemia-reperfusion injury in female rats. 1621 44

This study investigated the effects of the selective peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist WY14643 on ischemia/reperfusion (I/R) injury in the rat hippocampus. Transient cerebral ischemia (30 min), followed by 1-24 h reperfusion, significantly increased the generation of reactive oxygen species, nitric oxide (NO), and lipid peroxidation end-products, as well as markedly reducing levels of the endogenous antioxidant glutathione. Reperfusion for 3-6 h led to increased expression of the proteins heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1). Pretreatment with WY14643 suppressed oxidative stress and expression of HO-1, iNOS, and ICAM-1, but had no effect on COX-2. These effects are due to suppression of the activation of p38 mitogen-activated protein kinase and nuclear factor-kappaB. The PPAR-alpha antagonist MK886 abolished the beneficial effects of WY14643. The levels of S100B protein, a marker of cerebral injury used in stroke trials to monitor injury, were high in the hippocampus of rats exposed to I/R, but markedly reduced by WY14643. We propose that WY14643 protects the brain against excessive oxidative stress and inflammation and may thus be useful in treating stroke.
 ...
PMID:Oxidative stress and inflammatory response evoked by transient cerebral ischemia/reperfusion: effects of the PPAR-alpha agonist WY14643. 1686 91

Transient cerebral ischemia/stroke activates various post-translational protein modifications such as phosphorylation and ubiquitin conjugation that are believed to play a major role in the pathological process triggered by an interruption of blood supply and culminating in cell death. A new system of post-translational protein modification has been identified, termed as small ubiquitin-like modifier (SUMO) conjugation. Like ubiquitin, SUMO is conjugated to the lysine residue of target proteins in a complex process. This review summarizes observations from recent experiments focusing on the effect of cerebral ischemia on SUMO conjugation. Transient global and focal cerebral ischemia both induced a rapid, dramatic and long-lasting rise in levels of SUMO2/3 conjugation. After transient focal cerebral ischemia, SUMO conjugation was particularly prominent in neurons located at the border of the ischemic territory where SUMO-conjugated proteins translocated to the nucleus. Many SUMO conjugation target proteins are transcription factors and sumoylation has been shown to have a major impact on the activity, stability, and cellular localization of target proteins. The rise in levels of SUMO-conjugated proteins is therefore likely to have a major effect on the fate of post-ischemic neurons. The sumoylation process could provide an exciting new target for therapeutic intervention.
 ...
PMID:Cerebral ischemia/stroke and small ubiquitin-like modifier (SUMO) conjugation--a new target for therapeutic intervention? 1841 May 5

Transient cerebral ischaemia accompanies a number of disease processes, including stroke, subarachnoid haemorrhage and head injury, that have a profound social and economic impact on our community. The development of neuroprotective agents that reduce the morbidity associated with these diverse conditions requires an understanding of the mechanisms of neuronal death following cerebral ischaemia. There is increasing evidence that a significant proportion of neurons die following ischaemia by a process called apoptosis. Apoptosis involves the activation of a highly regulated series of intracellular events in which the neuron actively participates in its own death. Genes such as bcl-2 and proteolytic enzymes such as the caspases, which have been shown to play an important role in apoptotic cell death in other cell types, are now being investigated for their role in apoptotic neuronal death. This review will focus on current knowledge of the intracellular pathways of apoptosis, with particular reference to their role in ischaemic neuronal death.
 ...
PMID:Apoptotic neuronal death following cerebral ischaemia. 1863 1


1 2 3 Next >>