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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cognitive impairment from a major stroke as a consequence of carotid disease is an acknowledged clinical outcome; however, cognitive impairment without major stroke is open to discussion. The three recognized mechanisms for cognitive dysfunction from internal carotid artery are microembolization, white-matter disease, and hypoperfusion. The last has been most difficult to characterize physiologically. In this article, the authors review evidence supporting the existence of chronic ischemia in the brain and its direct impact on cognitive functions. By incorporating the pathophysiology of chronic ischemia into the algorithm of the management of carotid artery disease, we may be able to extend the goals of carotid artery revascularization beyond merely preventing stroke to include preventing or reversing cognitive decline.
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PMID:Chronic ischemia and neurocognition. 1782 34

Previous studies have demonstrated that Z-Ligustilide (LIG), a characterized phthalide constituent present in numerous medical Umbelliferae plants, has significant neuroprotective effects in transient forebrain ischemia and permanent cerebral focal ischemia. The present study further investigated the effect of LIG on chronic cerebral hypoperfusion. Male Wistar rats were subjected to permanent ligation of both common carotid arteries (2VO). On Days 8-12 postsurgery, rat cognition was assessed in the Morris water maze. Rats with significantly impaired acquisition of spatial information were randomly allocated to three groups and orally administered LIG (10 or 40 mg/kg/day) or volume-matched vehicle on Days 13-40 post-2VO surgery. The sham-operated group served as controls. After long-term treatment with LIG, the impaired animals' behavioral, biochemical, and histopathological features were examined. Compared to the sham-operated group, significant cognitive impairment was observed in the vehicle-treated group 40 days after 2VO. Shortened mean escape latency was detected in the Morris water maze in rats treated with LIG (p<0.01 vs. vehicle-treated group) during the same trial days. Chronic 2VO-induced pathological changes included neuronal loss and an increase of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in the hippocampus. These effects were prevented with LIG treatment (p<0.01 vs. vehicle-treated group). LIG also significantly reduced malondialdehyde levels and increased superoxide dismutase activity in ischemic brain tissue (p<0.05 and p<0.01 vs. vehicle-treated group). In addition, LIG significantly increased choline acetyltransferase activity and inhibited acetylcholinesterase activity in ischemic brain tissues (p<0.05 and p<0.01 vs. vehicle-treated group). The present data demonstrate that LIG significantly prevented chronically hypoperfused cognitive deficits and brain damage at least partly through an antioxidant effect and improved cholinergic activity. The present findings suggest that LIG may have therapeutic potential in treating vascular dementia and cerebrovascular insufficiency.
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PMID:Postischemic administration of Z-Ligustilide ameliorates cognitive dysfunction and brain damage induced by permanent forebrain ischemia in rats. 1788 86

Studies of retinal signs, as non-invasively obtained markers of microvasculature, may help to assess the microvascular contribution to ischemic cardiovascular diseases, particularly those affecting the brain. Changes in the retinal arterioles are particularly pertinent to ischemia, and several studies show their associations with MRI-assessed cerebral lacunar infarcts and white matter changes. Data are too sparse to judge the contribution to cerebral atrophy or cognitive impairment. Confounding and imprecise measurements may cloud the results of this research. A paired comparison method is proposed for avoiding some of these issues.
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PMID:A review of population-based retinal studies of the microvascular contribution to cerebrovascular diseases. 1789 3

Hypobaric hypoxia has been reported to cause memory dysfunction. The possible molecular mechanism involved, however, remains to be explored. The role that glutamate and its receptors play in causing excitotoxicity in ischemia and neurodegenerative diseases indicates the possible occurrence of a similar phenomenon in hypobaric hypoxia. The present study aimed to elucidate the molecular events occurring at glutamatergic synapses in hypobaric hypoxia using Sprague-Dawley rats as a model system. The animals were exposed to an altitude of 7,600 m for different durations. Hypobaric hypoxia was found to cause oxidative stress, chromatin condensation, and neurodegeneration. A temporal change in the expression of the ionotropic receptors of glutamate was also observed. Expression of the N-methyl-D-aspartate (NMDA) receptor increased, and expression of glutamate receptor subunit 2 of the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate receptor decreased. We also observed increased activity of glutamate dehydrogenase, indicating greater synthesis and release of glutamate after 3 and 7 days of exposure. Administration of a selective NMDA antagonist during exposure was found to ameliorate neuronal degeneration, providing evidence for the occurrence of excitotoxicity in hypobaric hypoxia. Our study indicates that excitotoxicity occurs in hypobaric hypoxia. This study also indicates the appropriate period for drug administration during exposure to hypobaric hypoxia and establishes ionotropic receptors of glutamate as potential therapeutic targets for ameliorating high-altitude-induced cognitive dysfunction.
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PMID:NR1 and GluR2 expression mediates excitotoxicity in chronic hypobaric hypoxia. 1796 5

Previous studies suggest that treatment with icariin (ICA) combined with Panax notoginseng saponins (PNS) improved behavior and cholinergic system disorders followed by amyloid beta-peptide(25-35) lateral ventricle injection in rats. The present study investigated whether administration of ICA + PNS had preventive and therapeutic effects on bilateral common carotid arteries (CCA) occlusion-induced cerebral ischemia-reperfusion (IR) injury in rats. Male Sprague-Dawley rats were divided randomly as follows: sham-operated, i.g. vehicle, ICA (5 mg/kg), PNS (40 mg/kg), ICA + PNS (2.5 + 20, 5 + 40 or 10 + 80 mg/kg), and ergoloid mesylate as a positive control (0.45 mg/kg) in model rats. Treatment was performed once a day for 7 days prior to ischemia. The rats were subjected to transient global IR induced by CCA occlusion in combination with intraperitoneal injection of sodium nitroprusside (2.0 mg/kg), then treated with ICA + PNS for another 14 days continuously. ICA + PNS significantly improved the rat passive avoidance task in step-down paradigms, and spatial cognition in the eight-arm radial maze, concomitant with an improvement of blood viscosity. Increased lipid peroxidation in brain after IR injury was observed, MDA being 0.56 +/- 0.10 nmol/mg prot vs 0.48 +/- 0.06 nmol/mg prot in the vehicle control (p < 0.05). Treatment with ICA + PNS 2.5 + 10, 5 + 40, 10 + 80 mg/kg produced a marked reduction in the MDA level to 0.46 +/- 0.06, 0.42 +/- 0.09 and 0.45 +/- 0.08 nmol/mg prot, respectively vs 0.56 +/- 0.10 nmol/mg prot in IR injury only control (p < 0.05, p < 0.01). A decrease in superoxide dismutase activity was observed in the brain of IR rats (the SOD activity being 72.75 +/- 4.62 U/mg prot vs 80.97 +/- 6.06 U/mg prot in control, p < 0.05). ICA + PNS 5 + 40 mg/kg prevented the IR injury mediated fall in superoxide dismutase activity being 78.90 +/- 6.61 U/mg prot versus 72.75 +/- 4.62 U/mg prot (p < 0.05). ICA + PNS tended to attenuate apoptosis in hippocampal CA1 pyramidal neurons. Either ICA or PNS treatment alone did not obviously improve cognitive impairment (except that lipid peroxidation was reduced by PNS-treatment). The results indicated that ICA + PNS may ameliorate learning and memory deficit and blood viscosity by protecting neurons from oxidative stress in ischemic brain.
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PMID:Effects of icariin combined with Panax notoginseng saponins on ischemia reperfusion-induced cognitive impairments related with oxidative stress and CA1 of hippocampal neurons in rat. 1839 27

Allon Therapeutics Inc is developing AL-108, an intranasally administered, eight-amino-acid peptide fragment (known as NAP) of activity-dependent neuroprotective protein, and AL-208, an intravenous formulation of NAP. AL-108 is undergoing phase II trials for cognitive impairment in Alzheimer's disease and schizophrenia. AL-108 is also being investigated as a neuroprotective agent, including for the treatment of Parkinson's disease and ocular disease. AL-208 is undergoing phase II clinical trials for the treatment of cognitive disorder and phase I clinical trials for ocular disease and cognitive deficits associated with coronary artery bypass graft or ischemia.
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PMID:AL-108 and AL-208, formulations of the neuroprotective NAP fragment of activity-dependent neuroprotective protein, for cognitive disorders. 1860 May 85

Although neurogenesis in the hippocampus is critical for improvement of depressive behaviors and cognitive functions in neurodegeneration disorders, there is no therapeutic agent available to promote neurogenesis in adult brain following brain ischemic injury. Here we found that i.p. administration of bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) [VO(OPT)], which stimulates phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal regulated kinase (ERK) pathways, markedly enhanced brain ischemia-induced neurogenesis in the subgranular zone (SGZ) of the mouse hippocampus. VO(OPT) treatment enhanced not only the number of proliferating cells but also migration of neuroblasts. VO(OPT)-induced neurogenesis was associated with Akt and ERK activation in neural precursors in the SGZ. Likewise, VO(OPT)-induced neurogenesis was blocked by both PI3K/Akt and mitogen-activated protein kinase/extracellular signal regulated kinase kinase (MEK)/ERK inhibitors. VO(OPT) treatment rescued decreased phosphorylation of glycogen synthesis kinase 3beta (GSK-3beta) at Ser-9. Finally, amelioration of cognitive dysfunction seen following brain ischemia was positively correlated with VO(OPT)-induced neurogenesis. Taken together, VO(OPT) is a potential therapeutic agent that enhances ischemia-induced neurogenesis through PI3K/Akt and ERK activation, thereby improving memory and cognitive deficits following brain ischemia.
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PMID:Bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) enhances neurogenesis via phosphatidylinositol 3-kinase/Akt and extracellular signal regulated kinase activation in the hippocampal subgranular zone after mouse focal cerebral ischemia. 1861 90

Cognitive deficits, including spatial memory impairment, are very common after ischemic stroke. Neurogenesis in the dentate gyrus (DG) contributes to forming spatial memory in the ischemic brain. Fluoxetine, a selective serotonin reuptake inhibitor, can enhance neurogenesis in the hippocampus in physiological situations and some neurological diseases. However, whether it has effects on ischemia-induced spatial cognitive impairment and hippocampal neurogenesis has not been determined. Here we report that fluoxetine treatment (10 mg kg(-1), i.p.) for 4 weeks promoted the survival of newborn cells in the ischemic hippocampus and, consequently, attenuated spatial memory impairment of mice after focal cerebral ischemia. Disrupting hippocampal neurogenesis blocked the beneficial effect of fluoxetine on ischemia-induced spatial cognitive impairment. These results suggest that chronic fluoxetine treatment benefits spatial cognitive function recovery following ischemic insult, and the improved cognitive function is associated with enhanced newborn cell survival in the hippocampus. Our results raise the possibility that fluoxetine can be used as a drug to treat poststroke spatial cognitive deficits.
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PMID:Chronic fluoxetine treatment improves ischemia-induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke. 1871 44

Local brain tissue oxygen (ptiO2) monitoring is frequently applied in patients at risk for cerebral ischemia. To identify ischemic thresholds, the normal range of local brain tissue oxygen pressure (ptiO2) values needs to be established. Ideally, such normal values are determined in healthy and awake subjects, so as to eliminate the possible influences of anesthetics on cerebral physiology or ptiO2. Thus far, however, such measurements have not been conducted, and to fill this void, we determined the ptiO2 values in normal white matter of awake patients undergoing functional stereotactic brain surgery. In 25 otherwise healthy patients, who underwent functional neurosurgery for treatment of a refractory movement disorder under local anesthesia, the ptiO2 of white matter was recorded continuously using a polarographic Clark type electrode monitoring system. Preoperative screening ruled out cognitive dysfunction or structural cerebral lesions. Reliable intraoperative ptiO2 values were obtained in 22 patients. After an adaptation period of 118+/-35 min (range, 47-171 min), we found an average normal ptiO2 of 22.6+/-7.2 mm Hg in the frontal white matter. In 11 patients, ptiO2 measurements were continued postoperatively for 24 h. During this period, a similar normal ptiO2 value of 23.1+/-6.6 mm Hg was found. No iatrogenic complications occurred. In conclusion, the normal ptiO2 of cerebral white matter is most likely lower than previously assumed. Further, the long adaptation time renders this widely applied monitoring instrument unreliable in detecting ischemia early after insertion and limits its usefulness for intraoperative monitoring.
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PMID:Brain tissue oxygen pressure monitoring in awake patients during functional neurosurgery: the assessment of normal values. 1884 78

The changes of visual, acoustic and cognitive evoked potentials of brain in 78 elderly patients were studied. Chronic ischemia of the heart and the brain with clinical signs of mild cognitive impairment was present in all patients. Distinct pathomorphologycal sings of structure disorders in brain were absent, and this fact was confirmed with the help of neuroimaging investigations. It was determined that deflections in the indexes of evoked potentials from the age according standard are objective and reliable diagnostic criterions both structural and functional changes in brain and initial cognitive deficit in the elderly patients with cardiovascular pathology. Authors offer complex examination of evoked potentials in diagnostics of the cognitive deficit and the functional separating between cortex and subcortical structures of brain.
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PMID:[Evoked potentials of the brain in early diagnostics of the cognitive disorders in the elderly patients with cardiovascular pathology]. 1894 80


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