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

The effects of oligemia (moderate ischemia) on the brain need to be explored because of the potential role of subtle microvascular changes in vascular cognitive impairment and dementia. Chronic bilateral common carotid artery occlusion (BCCAO) in adult rats has been used to study effects of oligemia (hypoperfusion) using neuropathological and neurochemical analysis as well as behavioral tests. In this study, BCCAO was induced for 1 week, or 2, 4, and 6 months. Sensitive immunohistochemistry with marker proteins was used to study reactions of astrocytes (GFAP, nestin), and lectin binding to study microglial cells during BCCAO. Overt neuronal loss was visualized with NeuN antibodies. Astrocytes reacted to changes in the optic tract at all time points, and strong glial reactions also occurred in the target areas of retinal fibers, indicating damage to the retina and optic nerve. Astrocytes indicated a change in the corpus callosum from early to late time points. Diffuse increases in GFAP labeling occurred in parts of the neocortex after 1 week of BCCAO, in the absence of focal changes of neuronal marker proteins. No significant differences emerged in the cortex at longer time points. Nestin labeling was elevated in the optic tract. Reactions of microglia cells were seen in the cortex after 1 week. Measurements of the basilar artery indicated a considerable hypertrophy, indicative of macrovascular compensation in the chronic occlusion model. These results indicate that chronic BCCAO and, by inference, oligemia have a transient effect on the neocortex and a long-lasting effect on white matter structures.
 ...
PMID:Astrocytes react to oligemia in the forebrain induced by chronic bilateral common carotid artery occlusion in rats. 1602 90

Transient global amnesia (TGA) is a disorder of unknown aetiology, characterized by sudden loss of anterograde memory, in the absence other neurological signs or symptoms, followed by complete recovery in less than 24h. Precipitating actions such as strenuous physical activity or valsalva-like manoeuvres are frequently reported. Since first described in 1958, by Fisher and Adams, the possible pathophysiology has undergone much speculation. Nonconvulsive epileptic seizures, migraine, paradoxical embolism thorough a patent foramen ovale, and transient ischemic attacks have been proposed as potential mechanisms. One of the latest hypotheses is that venous congestion causes either ischemia or induces spreading depression in the medial temporal lobes. It has been demonstrated that retrograde flow in the internal jugular veins occurs more frequently during valsalva manoeuvres in TGA patients than in controls, supporting a dysfunctional venous circulation as part of the pathogenesis. However, earlier hypotheses typically fail to explain the relatively low recurrence rate of TGA, lack of comorbidity and the relation to precipitating events. If cerebral venous hypertension was the solely cause of TGA it would presumably be much more common with very high recurrence rates among those predisposed of the condition. Structural changes observed in MRI and SPECT studies along with reports of mild cognitive impairment lasting much longer than the amnestic episodes, indicate that TGA is less transient and perhaps somewhat less benign than earlier believed. Many cases of TGA seem to be associated with factors of increased risk of cerebral venous thrombosis, such as polycythemia, antiphospholipid antibodies, venous hypertension, female sex and more. We suggest that most cases of TGA may be due to small thrombi in the deep cerebral venous system. Small venous thrombi may difficult to visualize even when using modern imaging technology. Further studies of TGA patients with for example blood analysis of D-dimer together with MR venography or CT venography could be done to evaluate this new hypothesis.
 ...
PMID:Transient global amnesia may be caused by cerebral vein thrombosis. 1606 28

The objective of this study was to establish a rodent model of vascular dementia that showed long-term cognitive and neuropsychological deficits, and to correlate those behavioral deficits with the patterns of ischemic lesions, thus providing a platform for future testing of potential therapeutic agents. In Mongolian gerbils, either 5-minute single bilateral common carotid artery occlusion (SBCCAO) or repetitive bilateral common carotid artery occlusion (two 7-minute occlusions, RBCCAO) was induced, and the behavioral deficits were evaluated using 2 tests: a modified open-field test with an escape zone to evaluate changes in anxiety and locomotor activity, and a T-maze test to assess cognitive dysfunction. SBCCAO did not induce anxiety changes but caused transient locomotor hyperactivity and mild cognitive deficits. Only pyramidal neuronal death was found in the bilateral CA1 sector of the hippocampus following SBCCAO. In contrast, RBCCAO induced persistent locomotor hyperactivity, reduced anxiety, and caused severe cognitive deficits at 4 weeks post-ischemia. RBCCAO caused significant atrophy associated with diffuse selective neuronal death in the bilateral cerebral cortex and caudate nucleus, as well as the CA1 region. The repetitive ischemia model appears to be a potentially useful platform for the long-term analysis of cognitive and neuropsychological symptoms associated with vascular dementia.
 ...
PMID:Long-term cognitive and neuropsychological symptoms after global cerebral ischemia in Mongolian gerbils. 1667 75

Hypoxic-ischemic encephalopathy accompanying cardiac arrest is a common cause of long-term neurological dysfunction. With the improvement in prehospital emergency systems, larger numbers of people are resuscitated from cardiac arrests, although with the increased prospect of neurological sequelae. Neurological impairment after cardiac arrest is dependent on the degree of brain damage suffered during the arrest. Although the duration and severity of brain ischemia is often difficult to determine, clinicians are often faced with difficult issues related to predicting outcome related to awakening and long-term neurological deficits after the arrest. Neurological impairments range from mild cognitive deficits to severe motor and cognitive deficits that preclude independence in many activities of daily living. Several neurological syndromes have been described in patients who awaken from hypoxic-ischemic coma with lasting motor and cognitive deficits. This review will address many of the common syndromes after hypoxic-ischemic encephalopathy, including persistent vegetative states, seizures, myoclonus, movement disorders, cognitive dysfunction, and other neurological abnormalities.
 ...
PMID:Long-term neurological complications after hypoxic-ischemic encephalopathy. 1696 43

Heterotrimeric guanine nucleotide-binding (G) protein-coupled receptor kinases (GRKs) are cytosolic proteins that are known to contribute to the adaptation of the heptahelical G protein-coupled receptors (GPCRs) and to regulate downstream signals through these receptors. GPCRs mediate the action of messengers that are key modulators of cardiac and vascular cell function, such as growth and differentiation. GRKs are members of a multigene family, which are classified into three subfamilies and are found in cardiac, vascular and cerebral tissues. Increasing evidence strongly supports the hypothesis that vascular damage is an early contributor to the development of Alzheimer disease (AD) and/or other pathology that can mimic human AD. Based on this hypothesis, and since kinases of this family are known to regulate numerous receptor functions both in the brain, myocardium and elsewhere, we explored cellular and subcellular localization by immunoreactivity of G protein-coupled receptor kinase 2 (GRK2), also known as beta-adrenergic receptor kinase-1(betaARK1), in the early pathogenesis of AD and in ischemia reperfusion injury models of brain hypoperfusion. In the present study, we used the two-vessel carotid artery occlusion model, namely the 2-VO system that results in chronic brain hypoperfusion (CBH) and mimics mild cognitive impairment (MCI) and vascular changes in AD pathology. Our findings demonstrate the early overexpression of GRK2 member kinase in the cerebrovasculature, especially endothelial cells (EC) following CBH, as well as in select cells from human AD tissue. We found a significant increase in GRK2 immunoreactivity in the EC of AD patients and after CBH, which preceded any amyloid deposition. Since GRK2 activity is associated with certain compensatory changes in brain cellular compartments and in ischemic cardiac tissue, our findings suggest that chronic hypoperfusion initiates oxidative stress in these conditions and appears to be the main initiating injury stimulus for disruption of brain and cerebrovascular homeostasis and metabolism.
 ...
PMID:Overexpression of GRK2 in Alzheimer disease and in a chronic hypoperfusion rat model is an early marker of brain mitochondrial lesions. 1700 Apr 69

The importance of hormone therapy in affording protection against the sequelae of global ischemia in postmenopausal women remains controversial. Global ischemia arising during cardiac arrest or cardiac surgery causes highly selective, delayed death of hippocampal CA1 neurons. Exogenous estradiol ameliorates global ischemia-induced neuronal death and cognitive impairment in male and female rodents. However, the molecular mechanisms by which estrogens intervene in global ischemia-induced apoptotic cell death are unclear. Here we show that estradiol acts via the classical estrogen receptors, the IGF-I receptor, and the ERK/MAPK signaling cascade to protect CA1 neurons in ovariectomized female rats and gerbils. We demonstrate that global ischemia promotes early dephosphorylation and inactivation of ERK1 and the transcription factor cAMP-response element binding protein (CREB), subsequent down-regulation of the antiapoptotic protein Bcl-2, a known gene target of estradiol and CREB, and activation of caspase-3. Estradiol treatment increases basal phosphorylation of both ERK1 and ERK2 in hippocampal CA1 and prevents ischemia-induced dephosphorylation and inactivation of ERK1 and CREB, down-regulation of Bcl-2 and activation of the caspase death cascade. Whereas ERK/MAPK signaling is critical to CREB activation and neuronal survival, the impact of estradiol on Bcl-2 levels is ERK independent. These findings support a model whereby estradiol acts via the classical estrogen receptors and IGF-I receptors, which converge on activation of ERK/MAPK signaling and CREB to promote neuronal survival in the face of global ischemia.
 ...
PMID:MAPK signaling is critical to estradiol protection of CA1 neurons in global ischemia. 1713 46

Clinical investigations designed to contrast the efficacy of carotid endarterectomy (CEA) versus best medical therapy and CEA versus carotid artery stenting (CAS) in patients with carotid artery stenosis have been based on the traditional endpoints of stroke, myocardial infarction, and death. Cognitive function is being increasingly recognized as an important outcome measure that affects patient well-being and functional status. However, it has not been evaluated systematically in the context of carotid revascularization. A decline in cognitive function could occur from microembolic ischemia during surgical dissection (CEA) or intravascular instrumentation (CAS). It could also occur from hypoperfusion during clamping (CEA) or balloon dilation (CAS). Conversely, restoring perfusion could improve cognitive dysfunction that might have occurred from a state of chronic hypoperfusion. It is still unclear whether these complex interactions ultimately result in a net improvement or a deterioration of cognitive function. Furthermore, it is not known whether the 2 methods of carotid revascularization have a differential effect on cognitive outcomes. It is becoming increasingly clear, though, that there is a positive relationship between improvement in cognition and improvement in functional outcome of patients. Vascular surgeons will be well served to remain informed and even actively engaged in the development of this field if they wish to continue providing the high-quality, well-informed care they have traditionally offered to patients with carotid stenosis.
 ...
PMID:Cognitive function after carotid artery revascularization. 1727 37

Spatial cognitive impairment is common after stroke insults. Voluntary exercise could improve the impaired spatial memory. Newly generated neurons in the dentate gyrus are necessary for the acquisition of new hippocampus-dependent memories. However, it is not well known whether voluntary exercise after stroke promotes neurogenesis in the adult dentate gyrus, thereby promoting spatial memory recovery. Here, we examined in mice subjected to focal cerebral ischemia the effect of voluntary or forced exercise on neurogenesis in the ischemic dentate gyrus and spatial memory. Exposure to voluntary wheel running after stroke enhanced newborn cell survival and up-regulated the phosphorylation of cAMP response element binding protein (CREB) in the dentate gyrus and reversed ischemia-induced spatial memory impairment. However, the enhanced newborn cell survival and CREB phosphorylation in the dentate gyrus and improved spatial memory were not observed in the mice exposed to forced swimming. Moreover, there was a significant correlation between the total number of surviving newborn cells in the dentate gyrus and the ability of mice to locate the platform in the Morris water maze. These results suggest that, in the adult mice, exposure to voluntary exercise after ischemic stroke may promote newborn cells survival in the dentate gyrus by up-regulating CREB phosphorylation and consequently restore impaired hippocampus-dependent memory.
 ...
PMID:Voluntary exercise-induced neurogenesis in the postischemic dentate gyrus is associated with spatial memory recovery from stroke. 1746 31

A growing body of evidence underscores the importance of early life events as predictors of health in adulthood. Abnormalities in maternal care or other forms of early postnatal stress induce long-term changes in behavior and influence the vulnerability to illnesses throughout life. Some of these changes may be produced by the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is invariably associated with stress. We used a model in which neonate rats are fed by mothers drinking water supplemented with 0.2 mg/ml corticosterone, the main glucocorticoid hormone in rodents. Plasma corticosterone levels increased in the dams to an extent similar to that induced by a mild stress. Corticosterone-treated dams also showed an increase in maternal care. Remarkably, adult rats that had been nursed by corticosterone-treated mothers were protected against neuronal damage and cognitive impairment produced by transient global brain ischemia. Neuroprotection was associated with a reduced HPA response to ischemia and was primarily decreased when corticosterone was injected at a dose that eliminated any difference in endogenous corticosterone levels between rats raised by mothers supplemented with corticosterone and their matched controls. These data suggest that an increased maternal care protects the offspring against ischemic neuronal damage and that at least a component of neuroprotection is mediated by a reduced response of the HPA axis to ischemia.
 ...
PMID:Maternal exposure to low levels of corticosterone during lactation protects the adult offspring against ischemic brain damage. 1759 53

Oxidative stress has been implicated to play a crucial role in the pathogenesis of a number of diseases, including neurodegenerative disorders, cancer, and ischemia, just to name a few. Alzheimer disease (AD) is an age-related neurodegenerative disorder that is recognized as the most common form of dementia. AD is histopathologically characterized by the presence of extracellular amyloid plaques, intracellular neurofibrillary tangles, the presence of oligomers of amyloid beta-peptide (Abeta), and synapse loss. In this review we discuss the role of Abeta in the pathogenesis of AD and also the use of redox proteomics to identify oxidatively modified brain proteins in AD and mild cognitive impairment. In addition, redox proteomics studies in in vivo models of AD centered around human Abeta(1-42) are discussed.
 ...
PMID:Roles of amyloid beta-peptide-associated oxidative stress and brain protein modifications in the pathogenesis of Alzheimer's disease and mild cognitive impairment. 1766 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>