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

Stroke is the third leading cause of death as dementia is a main symptom of Alzheimer's disease. One of the important mechanisms in the pathogeny of stroke is free radical production during the reperfusion period, therefore the effects of a type of natural antioxidant, i.e. Crataegus flavonoids (CF), on brain ischemic insults were investigated in Mongolian gerbil stroke model. Results showed that pretreatment of the animals with CF decreased reactive oxygen species (ROS) production, thiobarbituric acid reactive substances content, and nitrite/nitrate concentration in brain homogenate, increased the brain homogenate-associated antioxidant level in a dose-dependent manner. CF pretreatment increased the amount of biologically available NO by scavenging of superoxide anion produced during reperfusion. At same time, in the process of ischemia/reperfusion brain damage, the content of nitrite/nitrate (the end product of NO) increased, and of NO detected by ESR decreased. Oral pretreatment with CF decreased the nitrite/nitrate content in the brain homogenate and increased the biologically available NO concentration in a dose-dependent manner. The increasing effect of antioxidant on NO might be due to its scavenging effect on superoxide anion, which could react with NO into peroxynitrite. iNOS was implied in delayed neuron death after brain ischemic damage and it was found that pretreatment with CF could decrease the protein level of tumor necrosis factor (TNF)-alpha and nuclear factor-kappa B (NF-kappaB), and increase the mRNA level of NOS estimated by western blotting and RT-PCR. More neurons survived and fewer cells suffered apoptosis in the hippocampal CA1 region of CF treated animal brain. These results suggest that oral administration of this antioxidant increases the antioxidant level in the brain and protects the brain against delayed cell death caused by ischemia/reperfusion injury.
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PMID:Oral administration of Crataegus flavonoids protects against ischemia/reperfusion brain damage in gerbils. 1519 80

Ischaemic stroke is the second or third leading cause of death in developed countries. In the last two decades substantial research and efforts have been made to understand the biochemical mechanisms involved in brain damage and to develop new treatments. The evidence suggests that nitric oxide (NO) can exert both protective and deleterious effects depending on factors such as the NOS isoform and the cell type by which NO is produced or the temporal stage after the onset of the ischaemic brain injury. Immediately after brain ischaemia, NO release from eNOS is protective mainly by promoting vasodilation; however, after ischaemia develops, NO produced by overactivation of nNOS and, later, NO release by de novo expression of iNOS contribute to the brain damage. This review article summarizes experimental and clinical data supporting the dual role of NO in brain ischaemia and the mechanisms by which NO is regulated after brain ischaemia. We also review NO-based therapeutic strategies for stroke treatment, not only those directly linked with the NO pathway such as NO donors and NOS inhibitors but also those partially related like statins, aspirin or lubeluzole.
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PMID:Role of nitric oxide after brain ischaemia. 1526 82

We investigated the neuroprotective effects of a novel 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (pitavastatin) on ischemic neuronal damage in gerbils using immunohistochemistry. The animals were allowed to survive for 14 days after 5 min of ischemia induced by bilateral occlusion of the common carotid arteries. Five days after ischemia, severe neuronal cell loss was observed in the hippocampal CA1 sector. Prophylactic treatment with pitavastatin dose-dependently prevented the hippocampal CA1 neuronal cell loss 5 days after ischemia. Immunohistochemical study did not show the change of nNOS and iNOS expression in the hippocampus except for, in a few regions, up to 1 day after ischemia. Thereafter, the expression of iNOS was observed in the hippocampal CA1 sector 5 and 14 days after ischemia. In contrast, the expression of nNOS and eNOS gradually decreased in the hippocampal CA1 sector up to 14 days after ischemia. Prophylactic treatment with pitavastatin also prevented the expression of iNOS and the decrease of eNOS expression and the number of nNOS-positive cells in the hippocampal CA1 sector 5 days after ischemia. However, prophylactic treatment with pitavastatin at a dose of 10 mg kg(-1) did not change the immunoreactivity of iNOS and nNOS in the hippocampus at an early phase after ischemia. In contrast, this drug prevented the reduction of eNOS immunoreactivity in the hippocampal CA1 neurons at an early phase after ischemia. These findings demonstrate that the HMG-CoA reductase inhibitor pitavastatin can protect hippocampal CA1 neurons after transient forebrain ischemia through up-regulation of eNOS expression in this region. Thus pharmacological modulation of eNOS expression may offer a novel therapeutic strategy for cerebral ischemic stroke.
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PMID:Protective effect of pitavastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, on ischemia-induced neuronal damage. 1532 60

Newly developed insulin-sensitizing agents, which target the nuclear receptor peroxisome proliferator-activated receptor-gamma have recently been appreciated to exhibit potent anti-inflammatory actions. Since stroke is associated with an intense inflammatory response, we reasoned that these agents may ameliorate injury from stroke. We report that administration of troglitazone or pioglitazone 24 h before and at the time of cerebral infarction dramatically reduced infarction volume and improved neurological function following middle cerebral artery occlusion in rats. Furthermore, we find that delayed therapy also significantly reduced infarct volume. The brains of the drug-treated animals displayed reduced inflammation as evidenced by decreased immunoreactivity for microglial/macrophage markers and reduced protein and mRNA for interleukin-1beta, cyclooxygenase-2 and inducible nitric oxide synthase. We argue that the beneficial effects of these drugs are likely due to reduced expression of these inflammatory mediators, which are known to exacerbate ischemic injury following stroke. These results are of particular relevance to diabetic patients chronically treated with these agents who may benefit from the neuroprotective actions of these drugs.
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PMID:Peroxisome proliferator-activated receptor-gamma ligands reduce inflammation and infarction size in transient focal ischemia. 1559 Jan 52

Nitric oxide (NO) is produced in the CNS following injury-induced expression of inducible nitric oxide synthase (iNOS), yet its role as protective or damaging is unclear. Previous studies investigating the therapeutic potential of female sex steroids in stroke and trauma suggest that NO from this source is harmful, since oestradiol and progesterone decreased the level of iNOS expression in vitro and improved neurological outcome. We investigated the effects of progesterone on stroke-induced expression of iNOS in mice, as well as cytokine-induced expression of iNOS and its transcriptional activators in cells relevant to injury. We observed a significant reduction in stroke-induced iNOS transcript in progesterone-treated mice and in cultured macrophages. In contrast, progesterone significantly amplifed cytokine-induced iNOS mRNA in cultured primary astrocytes, although the expression of protein was decreased. We sequenced upstream of the 1.5 kb reported iNOS promoter region and identified a potential progesterone response element (PRE). Astrocytes transiently transfected with iNOS promoter/CAT reporter gene constructs containing the PRE displayed a significant increase in induction of CAT expression after progesterone treatment, and this was diminished in cells transfected with a construct containing a disrupted PRE. These observations suggest the involvement of iNOS in the neuroprotective effects of progesterone.
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PMID:Modulatory effects of progesterone on inducible nitric oxide synthase expression in vivo and in vitro. 1585 96

The aim of the present study was to ascertain whether the possible occurrence of overproduction of inducible nitric oxide synthase (iNOS)-dependent nitric oxide (NO) in the brain and inflammatory cytokines in the peripheral blood exhibited during heat stroke can be reduced by prior administration of Shengmai San, a Chinese herbal medicine. Aminoguanidine, an iNOS inhibitor, was evaluated at the same time as a reference (positive control). Urethane-anesthetized rats were exposed to heat stress (ambient temperature of 43 degrees C) to induce heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and cerebral blood flow after the onset of heat stroke were all significantly lower than in control rats. However, cerebral iNOS immunoreactivity and NO levels were all greater after the onset of heat stroke. The serum levels of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha were all increased after the onset of heat stroke. Shengmai San (1.2 g/ml per rat) or aminoguanidine (30 micromol/ml per rat) was administered orally, daily, and consecutively for 7 days before the initiation of heat stress; and this significantly attenuated the heat stress-induced arterial hypotension, cerebral ischemia, and increased levels of brain iNOS-dependent NO production and serum cytokines formation. Shengmai San shared with the aminoguanidine almost the same efficacy in reducing iNOS-dependent NO and cytokines overproduction during heat stroke. These results suggest that Shengmai San or aminoguanidine protects against heat stroke-induced arterial hypotension and cerebral ischemia by inhibition of iNOS-dependent NO overproduction in the brain and excessive accumulation of several inflammatory cytokines in the peripheral blood stream.
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PMID:Shengmai San, a Chinese herbal medicine protects against rat heat stroke by reducing inflammatory cytokines and nitric oxide formation. 1587 82

Nitric oxide produced by the neuronal or inducible isoform of nitric oxide synthase (nNOS, iNOS) is detrimental in acute ischemic stroke (IS), whereas that derived from the endothelial isoform is beneficial. However, experimental studies with nitric oxide synthase inhibitors have given conflicting results. Relevant studies were found from searches of EMBASE, PubMed, and reference lists; of 456 references found, 73 studies involving 2321 animals were included. Data on the effects of NOS inhibition on lesion volume (mm3, %) and cerebral blood flow (CBF; %, ml * min(-1) * g(-1)) were analyzed using the Cochrane Review Manager software. NOS inhibitors reduced total infarct volume in models of permanent (standardized mean difference (SMD) -0.56, 95% confidence interval (95% CI) -0.86, -0.26) and transient (SMD -0.99, 95% CI -1.25, -0.72) ischemia. Cortical CBF was reduced in models of permanent but not transient ischemia. When assessed by type of inhibitor, total lesion volume was reduced in permanent models by nNOS and iNOS inhibitors, but not by nonselective inhibitors. All types of NOS inhibitors reduced infarct volume in transient models. NOS inhibition may have negative effects on CBF but further studies are required. Selective nNOS and iNOS inhibitors are candidate treatments for acute IS.
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PMID:Nitric oxide synthase inhibitors in experimental ischemic stroke and their effects on infarct size and cerebral blood flow: a systematic review. 1599 40

The incidence of perinatal stroke is approximately 0.025%. About two thirds of these patients develop long-lasting neurological deficits. Preconditioning-induced neuroprotection, a phenomenon in which application of a stimulus induces brain ischemic tolerance, is investigated to improve outcome after a perinatal stroke. We applied prenatal hypoxia to fetuses by exposing 22-day pregnant mother rats to 15% oxygen for 30 min and subjected newborns with or without this prenatal hypoxia to brain ischemia 48 h later. Newborns with the prenatal hypoxia had a lower mortality rate, less brain tissue and neuronal loss and fewer active caspase 3 (an indicator for cell apoptosis) positive brain cells than newborns with the brain ischemia only. This neuroprotection was abolished by an inhibitor of inducible nitric oxide synthase (iNOS). The expression of iNOS proteins but not endothelial and neuronal NOS proteins was increased by the prenatal hypoxia. Thus, the prenatal hypoxia-induced neuroprotection may be iNOS-dependent.
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PMID:Prenatal hypoxia-induced adaptation and neuroprotection that is inducible nitric oxide synthase-dependent. 1599 93

Neurogenesis in the adult mammalian hippocampus may contribute to repairing the brain after injury. The signals that regulate neurogenesis in the dentate gyrus following ischemic stroke insult are not well known. We have previously reported that inducible nitric oxide synthase (iNOS) expression is necessary for ischemia-stimulated neurogenesis in the adult dentate gyrus. Here, we show that mice subjected to 90 min of middle cerebral artery occlusion (MCAO) significantly increased the number of new neurons and up-regulated iNOS expression in the dentate gyrus. Blockade of the L-type voltage-gated Ca(2+) channel (L-VGCC) prevented neurogenesis in the dentate gyrus and subventricular zone (SVZ), and down-regulated iNOS expression in the dentate gyrus after cerebral ischemia. This study suggests that Ca(2+) influx through L-VGCC is involved in ischemia-induced neurogenesis by up-regulating iNOS expression.
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PMID:Blockade of L-type voltage-gated Ca channel inhibits ischemia-induced neurogenesis by down-regulating iNOS expression in adult mouse. 1600 Jan 59

Activation of inflammatory mechanisms contributes to cerebrovascular pathophysiology. Male gender is associated with increased stroke risk, yet little is known about the effects of testosterone in the cerebral circulation. Therefore, we explored the impact of testosterone treatment on cerebrovascular inflammation with both in vivo and in vitro models of inflammation. We hypothesized that testosterone would augment the expression of two vascular markers of cellular inflammation, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Using four groups of male rats [intact, orchiectomized (ORX), and ORX treated with either testosterone (ORXT) or the testosterone metabolite 17beta-estradiol (ORXE)], we determined effects of the sex hormones on cerebrovascular inflammation after intraperitoneal LPS injection. Western blot analysis showed that induction of inflammatory markers was increased in cerebral blood vessels from ORXT rats compared with intact or ORX rats. In contrast, in cerebral blood vessels from ORXE rats, there was a significant decrease in endotoxin-induced COX-2 and iNOS protein levels. Confocal microscopy of cerebral blood vessels from ORXT rats showed increased COX-2 and iNOS immunoreactivity in both endothelial and smooth muscle cells after LPS treatment. In vitro incubation with LPS also induced COX-2 in pial vessels isolated from the four animal treatment groups, with the greatest induction observed in ORXT vessels compared with the ORX and ORXE groups. Production of PGE2, a principal COX-2-derived prostaglandin end product, was also greatest in cerebral vessels isolated from ORXT rats. In conclusion, testosterone increases cerebrovascular inflammation; this effect may contribute to stroke differences between men and women.
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PMID:Testosterone augments endotoxin-mediated cerebrovascular inflammation in male rats. 1600 44


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