Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to determine the minimum CBF and CMRO2 required by the human brain to maintain normal function and viability for more than a few hours. Positron emission tomography (PET) was used to perform regional measurements in 50 subjects with varying degrees of cerebral ischemia but no evidence of infarction. There were 24 normal subjects, 24 subjects with arteriographic evidence of vascular disease of the carotid system, and two subjects with reversible ischemic neurological deficits due to cerebral vasospasm. Minimum values found in the 48 subjects with normal neurological function were 19 ml/100 g-min for regional cerebral blood flow (rCBF) and 1.3 ml/100 g-min for regional cerebral metabolic rate of oxygen (rCMRO2). Minimum values for all 50 subjects with viable cerebral tissue were 15 ml/100 g-min for rCBF and 1.3 ml/100 g-min for rCMRO2. Comparison of these measurements with values from 20 areas of established cerebral infarction in 10 subjects demonstrated that 80% (16/20) of infarcted regions had rCMRO2 values below the lower normal limit of 1.3 ml/100 g-min. Measurements of rCBF, regional cerebral blood volume, and oxygen extraction fraction were less useful for distinguishing viable from infarcted tissue. These data indicate that quantitative regional measurements of rCMRO2 with PET accurately distinguish viable from nonviable cerebral tissue and may be useful in the prospective identification of patients with reversible ischemia.
J Cereb Blood Flow Metab 1985 Dec
PMID:Cerebral blood flow and cerebral metabolic rate of oxygen requirements for cerebral function and viability in humans. 387 67

A number of drugs used in the pharmacotherapy of cerebral metabolic and vascular disease have been studied for their effects on the respiration of mitochondria isolated from the rat brain. Some of these agents increased the respiratory control ratio by more than 5% from base-line values (at p less than 0.05), namely, aminophylline, dihydroergotoxine, ifenprodil, nicergoline, raubasine, and vincamine. The ability of these agents to increase the efficiency of mitochondrial respiration could be correlated with two other attributes peculiar to these five drugs: their ability to contract cerebrovascular smooth muscle when studied in vitro and their ability to decrease the volume of infarcted brain tissue following experimental occlusion of the middle cerebral artery in the cat. Papaverine and its derivatives (naftidrofuryl, viquidil, YC-93) decreased respiratory control, an effect that might correlate with their capacity to effect a vasodilatation of the cerebral vessels and their inefficacy in models of acute cerebral infarction. There is a considerable body of evidence suggesting that one of the earliest and most fundamental perturbations of cerebral ischaemia is a loss of respiratory control. Ifenprodil, vincamine, and some related "anti-ischaemic" compounds are capable of increasing respiratory control in normal cerebral mitochondria, and this capacity might well help to explain their therapeutic potential in cerebrovascular disorders in which energy supply to the brain is limited.
J Cereb Blood Flow Metab 1982
PMID:Effects of agents used in the pharmacotherapy of cerebrovascular disease on the oxygen consumption of isolated cerebral mitochondria. 706 2

Female reproductive hormones are considered to be protective agents in atherosclerotic vascular disease and stroke. The present study determined if there are unique cerebrovascular responses in female animals to global cerebral ischemia and if 17 beta-estradiol is important to postischemic outcome in brain. Three groups of anesthetized, sexually mature rabbits were treated with normotensive four-vessel occlusion (6 min) and 3 h of reperfusion: females chronically instrumented with 17 beta-estradiol implants (EFEM; n = 8, plasma estradiol level = 365 +/- 48 pg/ml), untreated females (FEM; n = 8, estradiol = 13 +/- 3 pg/ml), and untreated males (M; n = 8, estradiol < limit of radioimmunoassay). CBF (microspheres) and somatosensory evoked potential (SEP) amplitude were measured during ischemia/reperfusion. Baseline hemispheric blood flow and regional flow distribution were not altered by chronic estradiol treatment. Hemispheric blood flow was equivalently reduced during ischemia in FEM and M (6 +/- 1 and 9 +/- 2 ml min-1 100 g-1, respectively); however postischemic hyperemia was greater in FEM than M (CBF = 257 +/- 27 and 183 +/- 27 ml min-1 100 g-1. However, EFEM experienced higher CBF during ischemia (e.g., 13 +/- 2 ml min-1 100 g-1) and less hyperemia (134 +/- 4 ml min-1 100 g-1 in hemispheres) in numerous brain regions than FEM. CBF at 3 h reperfusion was not different among the groups. Recovery of SEPs was incomplete and similar in all groups. We conclude that chronic exogenous 17 beta-estradiol treatment increases CBF during global incomplete ischemia and ameliorates postischemic hyperemia in the female animal.
J Cereb Blood Flow Metab 1995 Jul
PMID:Postischemic cerebral blood flow recovery in the female: effect of 17 beta-estradiol. 779 Apr 16

Cytidine 5'-diphosphocholine, CDP-choline or citicoline, is an essential intermediate in the biosynthetic pathway of the structural phospholipids of cell membranes, especially in that of phosphatidylcholine. Upon oral or parenteral administration, CDP-choline releases its two principle components, cytidine and choline. When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously. Once absorbed, the cytidine and choline disperse widely throughout the organism, cross the blood-brain barrier and reach the central nervous system (CNS), where they are incorporated into the phospholipid fraction of the membrane and microsomes. CDP-choline activates the biosynthesis of structural phospholipids in the neuronal membranes, increases cerebral metabolism and acts on the levels of various neurotransmitters. Thus, it has been experimentally proven that CDP-choline increases noradrenaline and dopamine levels in the CNS. Due to these pharmacological activities, CDP-choline has a neuroprotective effect in situations of hypoxia and ischemia, as well as improved learning and memory performance in animal models of brain aging. Furthermore, it has been demonstrated that CDP-choline restores the activity of mitochondrial ATPase and of membranal Na+/K+ ATPase, inhibits the activation of phospholipase A2 and accelerates the reabsorption of cerebral edema in various experimental models. CDP-choline is a safe drug, as toxicological tests have shown; it has no serious effects on the cholinergic system and it is perfectly tolerated. These pharmacological characteristics, combined with CDP-choline's mechanisms of action, suggest that this drug may be suitable for the treatment of cerebral vascular disease, head trauma of varying severity and cognitive disorders of diverse etiology. In studies carried out on the treatment of patients with head trauma, CDP-choline accelerated the recovery from post-traumatic coma and the recuperation of walking ability, achieved a better final functional result and reduced the hospital stay of these patients, in addition to improving the cognitive and memory disturbances which are observed after a head trauma of lesser severity and which constitute the disorder known as postconcussion syndrome. In the treatment of patients with acute cerebral vascular disease of the ischemic type, CDP-choline accelerated the recovery of consciousness and motor deficit, attaining a better final result and facilitating the rehabilitation of these patients. The other important use for CDP-choline is in the treatment of senile cognitive impairment, which is secondary to degenerative diseases (e.g., Alzheimer's disease) and to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, CDP-choline improves scores on cognitive evaluation scales, while in patients with senile dementia of the Alzheimer's type, it slows the disease's evolution. Beneficial neuroendocrine, neuroimmunomodulatory and neurophysiological effects have been described. CDP-choline has also been shown to be effective as co-therapy for Parkinson's disease. No serious side effects have been found in any of the groups of patients treated with CDP-choline, which demonstrates the safety of the treatment.
 ...
PMID:CDP-choline: pharmacological and clinical review. 870 78

Although vascular dysregulation has been documented in patients with extracranial vascular disease, transient ischemic attacks, and stroke, the pathomechanisms are poorly understood. To model thromboembolic stroke in rats, photochemically induced nonocclusive common carotid artery thrombosis (CCAT) was used to generate a platelet thrombus in the carotid artery of anesthetized rats. After CCAT, platelet aggregates break off the thrombus, travel to the distal cerebral vasculature, damage blood vessels, and cause small infarctions. The authors hypothesized that deficits in the endothelial nitric oxide synthase (eNOS) pathway may be responsible for vascular dysfunction after embolic stroke. To examine the functional status of the eNOS system, they measured eNOS-dependent dilation after CCAT by applying acetylcholine through a cranial window over the middle cerebral artery. The authors also measured eNOS mRNA and protein in the middle cerebral artery to determine whether functional changes were caused by alterations in expression. eNOS-dependent dilation was reduced at 6 hours, elevated at 24 hours, and returned to baseline 72 hours after CCAT. Endothelial nitric oxide synthase mRNA increased at 2 hours and was followed by a rise in protein 24 hours after CCAT. Changes in the eNOS system may account for some of the observed vascular deficits in patients with cerebrovascular disease.
J Cereb Blood Flow Metab 2002 May
PMID:Endothelial nitric oxide synthase pathophysiology after nonocclusive common carotid artery thrombosis in rats. 1197 34

Erythropoietin (EPO) plays a prominent role in the regulation of the hematopoietic system, but the potential function of this trophic factor as a cytoprotectant in the cerebral vascular system is not known. The authors examined the ability of EPO to modulate a series of death-related cellular pathways during free radical-induced injury in cerebral microvascular endothelial cells (ECs). Endothelial cell injury was evaluated by trypan blue, DNA fragmentation, membrane phosphatidylserine exposure, apoptotic protease-activating factor-1 (Apaf-1), and Bcl-XL expression, mitochondrial membrane potential, cytochrome c release, and cysteine protease activity. They show that constitutive EPO is present in ECs but is insufficient to prevent cellular injury. Signaling through the EPO receptor, however, remains biologically responsive to exogenous EPO administration to offer significant protection against nitric oxide-induced injury. Exogenous EPO maintains both genomic DNA integrity and cellular membrane asymmetry through parallel pathways that prevent the induction of Apaf-1 and preserve mitochondrial membrane potential in conjunction with enhanced Bcl-XL expression. Consistent with the modulation of Apaf-1 and the release of cytochrome c, EPO also inhibits the activation of caspase-9 and caspase-3-like activities. Identification of novel cytoprotective pathways used by EPO may serve as therapeutic targets for cerebral vascular disease.
J Cereb Blood Flow Metab 2003 Mar
PMID:Apaf-1, Bcl-xL, cytochrome c, and caspase-9 form the critical elements for cerebral vascular protection by erythropoietin. 1262 7

Cerebrovascular reserve (CVR) and oxygen extraction fraction (OEF) are used to identify hemodynamic compromise in symptomatic patients with carotid occlusive vascular disease, but evidence suggests that they are not equivalent. The authors studied the relationship between CVR and OEF to evaluate their equivalence and stages of hemodynamic compromise. Symptomatic patients (N = 12) with carotid occlusion were studied by stable xenon-computed tomography CBF after intravenous acetazolamide administration for CVR, followed within 24 hours by positron emission tomography (PET) for OEF. Middle cerebral artery territories were analyzed by hemisphere and level. Hemispheric subcortical white matter infarctions were graded with magnetic resonance imaging. Both hemispheric and level analysis of CVR and OEF showed a significant (P = 0.001), negative linear relationship [CVR (%) = -1.5 (OEF) + 83.4, (r = -0.57, P = 0.001, n = 24]. However, 37.5% of the hemispheres showed compromised CVR but normal OEF and were associated (P = 0.019) with subcortical white matter infarction. CMRO2 was elevated in stage II hemodynamic compromise (CVR < 10%, OEF > 50%). CVR and OEF showed a significant negative linear relationship in stage II hemodynamic compromise but revealed hemispheres in hemodynamic compromise by CVR but normal OEF that were associated with subcortical white matter infarction.
J Cereb Blood Flow Metab 2004 Oct
PMID:Identification of hemodynamic compromise by cerebrovascular reserve and oxygen extraction fraction in occlusive vascular disease. 1552 8

Inhibitors of HMG-CoA reductase (statins) are potent cholesterol-lowering drugs. Large clinical trials have shown that statins reduce the incidence of cerebrovascular events, which might be surprising because cholesterol is not an established risk factor for stroke. In addition to their cholesterol-lowering properties, statins exert a number of pleiotropic, vasculoprotective actions that include improvement of endothelial function, increased nitric oxide (NO) bioavailability, antioxidant properties, inhibition of inflammatory responses, immunomodulatory actions, regulation of progenitor cells, and stabilization of atherosclerotic plaques. In fact, statins augment cerebral blood flow and confer significant protection in animal models of stroke partly via mechanisms related to the upregulation of endothelial nitric oxide synthase. Retrospective clinical evidence suggests that long-term statin administration may not only reduce stroke risk but also improve outcome. Early secondary prevention trials are underway to test the hypothesis that statin treatment initiated immediately after an event improves short-term outcome. Lastly, recent evidence suggests that sudden discontinuation of statin treatment leads to a rebound effect with downregulation of NO production. Withdrawal of statin treatment may impair vascular function and increase morbidity and mortality in patients with vascular disease.
J Cereb Blood Flow Metab 2005 Sep
PMID:Statins and stroke. 1581 80

The amyloid-beta peptide (Abeta) induces apoptosis in cerebrovascular endothelial cells (CECs), contributing to the pathogenesis of cerebral amyloid angiopathy. We have previously shown that Abeta induces apoptosis in CECs. In the present study, we report that Abeta25-35-induced CEC apoptosis involves the inactivation of Akt, a signaling kinase important in maintaining cell viability. Akt prevents the activation of death-signaling events by facilitating the inactivation of proapoptotic proteins such as Bad. We applied three strategies to show that Abeta25-35 inactivation of Akt is causally related to Abeta25-35-induced CEC death by preventing Bad activation and subsequent mitochondrial dysfunction (reflected by the release of endonuclease G and Smac, two proapoptotic intermembranous proteins of the mitochondria). Wortmannin, a PI3-kinase inhibitor, enhanced Abeta25-35-induced Bad activation, mitochondrial dysfunction and CEC death. Enhancement of Akt activity by a Tat-Akt fusion protein, or by viral gene transfer of a constitutively active mutant of akt, reduced Bad activation, mitochondrial dysfunction, and CEC death. Using a siRNA strategy to knock down the bad gene, we showed that Bad activation is causally related to Abeta25-35-induced mitochondrial dysfunction and CEC death. Together, these results establish that the Akt-Bad cascade is altered by Abeta25-35, resulting in CEC apoptosis.
J Cereb Blood Flow Metab 2005 Nov
PMID:Abeta25-35 alters Akt activity, resulting in Bad translocation and mitochondrial dysfunction in cerebrovascular endothelial cells. 1597 55

We examined whether the degree of hemodynamic stress in patients with chronic occlusive cerebral vascular disease can be quantitatively evaluated with the use of perfusion-weighted magnetic resonance imaging (PWI). Thirty-six patients with moyamoya disease (mean age, 26.8 years; range, 18 to 59) underwent PWI and positron emission tomography (PET) within a month's interval. The PWI data were calculated by three different analytic methods. The cerebral blood flow (CBF) ratio, cerebral blood volume (CBV) ratio, and mean transit time (MTT) of the anterior circulation were calculated using the cerebellum as a control region and compared with PET data on the same three parameters and oxygen extraction fraction (OEF). Parametric maps of PWI attained a higher resolution than the PET maps and revealed focal perfusion failure on a gyrus-by-gyrus level. The relative CBV and MTT obtained with PWI showed significant linear correlations with the corresponding PET values (CBV, R2 = 0.47 to 0.58; MTT, R2 = 0.32 to 0.68). We also found that we could detect regions with abnormally elevated OEF and CBV based on the delay of PWI-measured MTT relative to the control region by defining a 2.0-sec delay as a threshold. The sensitivity and specificity were 92.3% and 100% in detecting regions with abnormally elevated OEF, and 20.0% and 100% in detecting regions with abnormally elevated CBV, respectively. Among the parameters obtained with PWI, our results suggested that the relative CBV value and delay of MTT might be quantitatively manipulated to assist in clinical decision-making for patients with moyamoya disease.
J Cereb Blood Flow Metab 2006 Feb
PMID:Quantitative evaluation of cerebral hemodynamics in patients with moyamoya disease by dynamic susceptibility contrast magnetic resonance imaging--comparison with positron emission tomography. 1604 27


1 2 3 4 5 6 Next >>