Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, we have become increasingly aware that estrogen is a gonadal hormone that exerts diverse non-reproductive actions on multiple organs and in multiple physiological systems. Amongst these, estrogen has profound effects on plasticity and cell survival of the adult brain. Over the past 100 years, the lifespan of women has increased to >80 years, but the age of the menopause has remained fixed. Women are therefore living an ever-increasing proportion of their lives in a hypoestrogenic, postmenopausal state, which could contribute to an increased risk of cognitive dysfunction and a variety of neurodegenerative diseases. Recent experiments emphasize the importance of apoptosis as a mechanism of cell death after brain injury induced by global ischemia, and indicate that estrogen treatment has a neuroprotective effect by attenuating expression of selective markers of apoptosis.
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PMID:Estrogens and neuroprotection. 1212 78

It is of interest whether the acetylcholinesterase inhibitor, 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147), can improve cognitive impairment caused by chronic cerebral ischemia in rats. Two weeks after four-vessel occlusion, apparent impairments of spatial retrieval memory were observed in the Morris water maze. Both TAK-147 at doses of 0.1, 0.3 and 1.0 mg/kg and donepezil at doses of 0.3 and 1.0 mg/kg significantly ameliorated ischemia-induced memory deficits dose-dependently, but tacrine had no appreciable effect. Furthermore, we demonstrate that the intensity of staining by 2,3,5-triphenyltetrazolium in the hippocampal and cortical slices was significantly decreased by ischemia (10 min anoxia/aglycemia), and that it was also significantly restored by treatment with TAK-147 and donepezil.
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PMID:Effect of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate, a novel acetylcholinesterase inhibitor, on spatial cognitive impairment induced by chronic cerebral hypoperfusion in rats. 1235 17

Cerebrovascular lesions, mainly lacunes and white matter ischemia, are common in elderly patients with dementia. Vascular dementia (VaD) is the second most common cause of dementia, after Alzheimer's disease (AD). However, lacunar strokes have become an important factor in the clinical expression of AD. Also, population-based studies indicate that vascular risk factors increase the risk of developing AD. It is postulated here that the two main causes of VaD-stroke and ischemic heart disease (IHD)-may be responsible for the majority of cases of dementia in the elderly. STROKE RELATED VaD: Cerebrovascular disease (CVD) is the second leading cause of death worldwide. About 1/3 of stroke survivors [range: 25-41%] 65 years old and above develop VaD within 3 months following the ictus. In the USA alone, 125,000 new cases/year of VaD occur after ischemic stroke (about 1/3 of the 360,000 incident cases of AD). Therefore, more than 1 million elderly people are currently affected by poststroke VaD in the USA. Since current criteria identify "pure" cases of AD and VaD, it is likely that "AD plus CVD" ("mixed" dementia) could be responsible for a large number of cases currently diagnosed as probable AD. CARDIOGENIC VAD: By 2020, IHD leading to congestive heart failure (CHF) will become the leading cause of disability worldwide. Vascular cognitive impairment occurs in 26% of patients discharged from hospitals after treatment for CHF. Cognitive dysfunction correlates with left ventricular dysfunction and systolic blood pressure below 130 mm Hg. CHF is a leading cause of hospital admissions in Western nations (4.5 million cases in the USA alone) and is a growing problem in developing countries. Furthermore, over 800,000 patients/year undergo coronary artery bypass graft (CABG) surgery worldwide, including 300,000 patients in the USA. Measurable cognitive dysfunction occurs post-CABG in 80-90% of patients at hospital discharge. Long-term (5 years) incidence of cognitive defects is 42%. Finally, an international study found short-term postoperative cognitive dysfunction in 26% of patients (>60 years) after abdominal or orthopedic surgery; most of them may be instances of VaD. In conclusion, VaD may be the most underdiagnosed and undertreated form of dementia in the elderly.
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PMID:Vascular dementia may be the most common form of dementia in the elderly. 1241 49

Chronic brain hypoperfusion (CBH) using permanent occlusion of both common carotid arteries in an aging rat model, has been shown to mimic human mild cognitive impairment (MCI), an acknowledged high risk condition that often converts to Alzheimer's disease. An aging rat model was used to determine whether hippocampal nitric oxide (NO) is abnormally expressed following CBH for two or eight weeks. At each time point, spatial memory was measured with the Morris water maze and hippocampal A beta 1-40/1-42 concentrations were obtained using sandwich ELISA. Real-time amperometric measures of NO representing the constitutive isoforms of neuronal nitric oxide synthase (nNOS) and endothelial (e)NOS were also taken at each time point to ascertain whether NO levels changed as a result of CBH, and if so, whether such NO changes preceded or followed any memory or amyloid-beta pathology. We found that two weeks after CBH, NO hippocampal levels were upregulated nearly four-fold when compared to nonoccluded rats but no alteration in spatial memory of A beta products were observed at this time point. By contrast, NO concentration had declined to control levels by eight weeks but spatial memory was found significantly impaired and A beta 1-40 (but not A beta 1-42) had increased in the CBH group when compared to control rats. Since changes in shear stress are known to upregulate eNOS but generally not nNOS, these results suggest that shear stress induced by CBH hyperactivated vascular NO derived from eNOS in the first two weeks as a reaction by the capillary endothelium to maintain homeostasis of local cerebral blood flow. The return of vascular NO to basal levels after eight weeks of CBH may have triggered metabolic changes within hippocampal cells resulting in hippocampal dysfunction as reflected by spatial memory impairment and by accumulation of A beta 1-40 peptide. In conclusion, our study shows that CBH initiates spatial memory loss in aging rats thus mimicking human MCI and also increases A beta 1-40 in the hippocampus. The memory and amyloid changes are preceded by NO upregulation in the hippocampus. These preliminary findings may be important in understanding, at least in part, the molecular mechanisms that precede memory impairment during chronic brain ischemia and as such, the pre-clinical stage leading to Alzheimer's disease.
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PMID:Hippocampal nitric oxide upregulation precedes memory loss and A beta 1-40 accumulation after chronic brain hypoperfusion in rats. 1450 18

Chronic cerebrovascular ischemia is an important cerebrovascular disorder leading to progression of the functional neurological deficite--to cognitive impairment in the first place. The main reason for the above condition is a stenotic affection of major arteries of the head. In the treatment of patients presenting with the above pathology, we used mildronate (10% infusion solution, 10 ml, for up to 10 days followed by tablets, 750 mg per day for 20 days). As clinical and paraclinical monitoring was conducted of the condition of patients with making use of X-ray computerized tomography, electroencephalography, ultrasonic dopplerography of extra- and intracranial arteries, an assessment was done of findings from the neuropsychological testing. A positive effect is shown on the degree of neurological symptomatology, hemodynamic, electrophysiological, neuropsychological characteristics of the pathology in question. The drug is recommended for use in the treatment of stage II chronic cerebrovascular insufficiency originated and gone ahead because of a stenotic affection of major arteries of the head.
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PMID:[Use of mildronate for the treatment of patients with circulatory encephalopathy against a background of stenosis of major arteries of the head]. 1461 18

The behavioral and neurohistological protective effects of tacrolimus (FK506) were examined in rats subjected to 15-min global forebrain ischemia. Learning and memory performance were evaluated in an aversive, non-food-motivated, eight-arm radial maze. In one experiment, naive rats were rendered ischemic, and 15 days later they were tested for acquisition of a spatial task (postoperative training). In a complementary experiment, rats were trained for 8 days and then subjected to ischemia (preoperative training); 15 days later (on Day 24 of testing) they were retested for retention of cognition. FK506 (1.0 mg/kg) was given intravenously at the beginning of reperfusion, followed by doses applied intraperitoneally 6, 24, 48 and 72 h postischemia. Behavioral performance was expressed by latency to find the goal box, and number of errors. Ischemia did not affect acquisition performance. In contrast, retention of cognition was markedly impaired by ischemia, particularly working memory (P<.05-.001). This ischemia-induced, retrograde amnesia was significantly reduced by FK506 compared to vehicle alone on Day 24, as measured by latency and working memory errors (P<.025). A neuroprotective effect of FK506 was also seen on working memory, when postischemic performance was compared to that prior to ischemia (P>.05, Day 24 vs. Day 8, paired samples), in contrast to the significant, retrograde amnesia found in the ischemic, vehicle-treated group (P<.01). FK506 also significantly reduced the extent of hippocampal CA1 cell loss; however, this effect did not correlate with behavior. The present results suggest that the histological, neuroprotective effect of FK506 may be accompanied by a reduction in cognitive impairment, as assessed in a novel, non-food-motivated, eight-arm radial maze after transient, global, cerebral ischemia in rats.
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PMID:Effect of tacrolimus (FK506) on ischemia-induced brain damage and memory dysfunction in rats. 1500 73

Dural fistulas are acquired arteriovenous shunts, accounting for 10-15p.cent of cerebrovascular malformations. Symptoms are commonly tinnitus or intracranial hemorrhage. Rarely, patients with dural fistulas can present with rapid cognitive impairment. We report two women with rapidly evolving dementia. Cerebral angiography revealed dural arteriovenous fistula, with retrograde drainage into cortical veins, related to thrombosis of both transverse sinuses. Intra-arterial and intra-venous endovascular approaches failed to cure the fistula. Venous embolization via a transcranial approach was required to occlude the fistula, leading to resolution of the symptoms. Dural arteriovenous fistulas may lead to dementia with diffuse white matter changes related to venous ischemia, and must be considered as a reversible cause of vascular dementia. A transcranial approach for venous embolization is sometimes required.
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PMID:[Dural arteriovenous fistula. A rare cause of treatable dementia]. 1510 67

The hippocampal formation, a structure involved in declarative, spatial and contextual memory, undergoes atrophy in depressive illness along with impairment in cognitive function. Animal model studies have shown that the hippocampus is a particularly sensitive and vulnerable brain region that responds to stress and stress hormones. Studies on models of stress and glucocorticoid actions reveal that the hippocampus shows a considerable degree of structural plasticity in the adult brain. Stress suppresses neurogenesis of dentate gyrus granule neurons, and repeated stress causes remodeling of dendrites in the CA3 region, a region that is particularly important in memory processing. Both forms of structural remodeling of the hippocampus are mediated by adrenal steroids working in concert with excitatory amino acids (EAA) and N-methyl-D-aspartate (NMDA) receptors. EAA and NMDA receptors are also involved in neuronal death that is caused in pyramidal neurons by seizures, head trauma, and ischemia, and alterations of calcium homeostasis that accompany age-related cognitive impairment. Tianeptine (tianeptine) is an effective antidepressant that prevents and even reverses the actions of stress and glucocorticoids on dendritic remodeling in an animal model of chronic stress. Multiple neurotransmitter systems contribute to dendritic remodeling, including EAA, serotonin, and gamma-aminobutyric acid (GABA), working synergistically with glucocorticoids. This review summarizes findings on neurochemical targets of adrenal steroid actions that may explain their role in the remodeling process. In studying these actions, we hope to better understand the molecular and cellular targets of action of tianeptine in relation to its role in influencing structural plasticity of the hippocampus.
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PMID:Structural plasticity and tianeptine: cellular and molecular targets. 1517 88

Cerebrovascular disease (CVD), as well as secondary ischemic brain injury from cardiovascular disease, are common causes of dementia and cognitive decline in the elderly. Also, CVD frequently contributes to cognitive loss in patients with Alzheimer's disease (AD). Progress in understanding the pathogenetic mechanism involved in vascular cognitive impairment and vascular dementia (VaD) has resulted in promising treatments of these conditions. Cholinergic deficits in VaD are due to ischemia of basal forebrain nuclei and of cholinergic pathways and can be treated with the use of the cholinesterase inhibitors used in AD. Controlled clinical trials with donepezil, galantamine, and rivastigmine in VaD, as well as in patients with AD plus CVD, have demonstrated improvement in cognition, behavior and activities of daily living.
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PMID:Treatment of vascular dementia-evidence from clinical trials with cholinesterase inhibitors. 1526 82

We reported previously that chronic hypoperfusion induced by permanent occlusion of the bilateral common carotid arteries (2VO) in rats caused progressive cognitive deficits and neuronal damage in the hippocampus and the white matter. These changes are similar to those observed in human dementia. Reverse transcription-polymerase chain reaction (RT-PCR) differential display was carried out to identify mRNAs encoding the intrinsic factors involved in permanent ischemia from the 2VO rat brain. Over 20 clones which showed different expression levels in 2VO and sham-operated rats were isolated. One of these, named vof-16, was markedly enhanced the expression by 2VO. The whole sequence of vof-16 mRNA was 2098 nt. The distribution of vof-16 transcripts was examined by RT-PCR and in situ hybridization. The results revealed that vof-16 was abundant in the hippocampus, the tenia tecta, the piriform cortex and the area around the aorta. The expression levels of vof-16 in 2VO and sham-operated rat hippocampus were determined by a quantitative PCR method. The expression was abundant in the hippocampus of rats with cognitive impairment induced by 2VO. In contrast, the expression levels of vof-16 were lower in the 2VO rats with no impairment and in sham-operated rats. These results suggest that the expression levels of vof-16 may be related to the cognitive impairment induced by chronic ischemia after 2VO.
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PMID:Molecular cloning and characterization of a novel sequence, vof-16, with enhanced expression in permanent ischemic rat brain. 1530 27


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