Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotropic peptide growth factor. The expression of TGF-beta 1 mRNA in the focal ischemic cortex of rats was studied by means of Northern hybridization. A moderately low level of constitutively expressed TGF-beta 1 mRNA was detected following sham-surgery or in the contralateral (nonischemic) cortex. A significant increase of TGF-beta 1 mRNA level in the ischemic cortex was observed at 2 days (3.2-fold increase compared to sham-operated animals, p < 0.01, n = 4) following permanent occlusion of the middle cerebral artery (PMCAO). The elevated TGF-beta 1 mRNA expression was plateaued for up to 15 days (3.6-fold increase, p < 0.01) following PMCAO. This temporal profile for TGF-beta 1 mRNA expression in focal stroke was significantly delayed compared to that of TNF-alpha, IL-1 beta and IL-6 mRNA expressions as demonstrated previously which peaked at 12 h and decreased to almost basal levels by 5 days following PMCAO. Interestingly, the TGF-beta 1 mRNA expression profile was remarkably parallel with that of monocyte/macrophage accumulation in the ischemic cortex, as well as with the increased formation of extracellular matrix in the focal ischemic brain. These data suggest that TGF-beta 1 may play a role in anti-inflammatory process and in tissue remodeling following ischemic brain injury.
 ...
PMID:Transforming growth factor-beta 1 exhibits delayed gene expression following focal cerebral ischemia. 775 96

There is evidence that leukocytes play an important role in mediating tissue injury during acute ischemic stroke. Endothelial cell adhesive molecules such as ICAM-1 are required for the migration of leukocytes into the brain. Using an Elisa, we compared the expression of ICAM-1 by human brain microvascular endothelial cells with human umbilical vein endothelial cells. There was constitutive surface expression of ICAM-1 on both brain and umbilical vein endothelial cells. With cytokine (IL-1 beta or TNF) or lipopolysaccaride stimulation, ICAM-1 surface expression increased to a greater extent on brain than on umbilical vein endothelial cells. Dexamethasone at doses up to 100 microM had no effect on inhibiting cytokine-mediated upregulation of ICAM-1 on human brain microvascular endothelial cells.
 ...
PMID:ICAM-1 expression on human brain microvascular endothelial cells. 791 16

Heat stroke is a disease characterized by high fever. Cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-delta) play a major role in fever production. In the current studies, eight patients with heat stroke were enrolled in a cytokine studies. Serum cytokine levels of these patients were determined by EIA methods, and in vitro IL-1 and IL-1 inhibitor production were determined by murine thymocyte proliferation assay and/or EIA. Significantly high levels of circulating IL-1, TNF-delta, and IL-6 were demonstrated. Positive correlations were demonstrated between the body temperature and the level of IL-1 beta, and the cooling time and level of serum IL-1 beta. In addition, monocytes from heat stroke patients after complete recovery, secreted a much higher amount of IL-1 than did normal volunteers. However, there was no difference in IL-1 inhibitor production. These results indicate that cytokines may play a major role in the pathogenesis of heat stroke, and the ability to make different amounts of IL-1 in response to exogenous stimulation appear to be risk factors for an attack of heat stroke.
 ...
PMID:The role of cytokines in heat stroke. 830 Jan 62

Interleukin (IL)-1 beta-converting enzyme (ICE) cleaves the biologically inactive precursor form of IL-1 beta into mature, bioactive IL-1 beta. Because of the potent effects of IL-1 in blood vessels, we conducted an in situ hybridization study to determine whether ICE mRNA is constitutively expressed in adult rat brain vasculature. Using in situ hybridization histochemistry, we were able to demonstrate that mRNA in blood vessels scattered throughout the brain. In a second set experiments, we found that the genes encoding not only ICE, but also IL-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1ra), and the IL-1 type I receptor are expressed in brain vasculature. To our knowledge this is the first report documenting the expression of the genes encoding all of the functional elements of the IL-1 system in the same tissue. Our findings have three pathophysiological implications. First, they indicate a possible site where peripheral IL-1 may act in the brain. The vascular IL-1 system stimulates the production of nitric oxide and prostanoids, which could act as mediators of the effects of peripheral IL-1 in the central nervous system. Additionally, vascular IL-1 is known to activate adhesion molecules; our data that the genes encoding the IL-1 system are expressed in brain vasculature further support the concept that IL-1 is implicated in the pathophysiology of atherosclerosis and stroke. Finally, in the context of previous studies documenting that IL-1ra inhibits the effects of IL-1 on endothelial cells, our findings of endogenous IL-1ra mRNA in brain vasculature indicate that IL-1ra might be an endogenous vascular protective agent.
 ...
PMID:Localization of interleukin-1 beta converting enzyme mRNA in rat brain vasculature: evidence that the genes encoding the interleukin-1 system are constitutively expressed in brain blood vessels. Pathophysiological implications. 864 63

The cytokines are multipotent mediators of inflammation and immunity that can affect key functions of vascular wall cells. Growing evidence suggests that cytokines participate as autocrine or paracrine mediators in atherogenesis, as cells in lesions can both produce and respond to these mediators. The functions of vascular wall cells regulated by cytokines may influence lesion initiation, progression, or complication. For example, cytokines can regulate the expression of adhesion molecules crucial to the recruitment of leukocytes to lesions, including vascular cell adhesion molecule-1 (VCAM-1). Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) can regulate the production of monocyte chemoattractant protein-1 (MCP-1), a potential signal for directed migration of monocytes into the intima. Cytokines can also regulate genes that encode other growth factors and cytokines themselves. TNF-alpha can induce IL-1 mRNA in human endothelial (EC) and smooth-muscle cells (SMC). IL-1 and TNF-alpha can augment the production by vascular cells of macrophage-colony stimulating factor (M-CSF), which may promote growth and activation of mononuclear phagocytes. Cytokines can exert both pro-and antiatherogenic actions. Activated T cells in human atheroma may secrete the lymphokine IFN-gamma, an inhibitor of SMC proliferation. Cytokines influence vasomotor tone in arteries, e.g., by inducing a form of nitric oxide synthase, the enzyme that synthesizes the vasodilatory nitric oxide radical. The cytokines also modulate endothelial functions that govern the formation and stability of blood thrombi. Finally, in the late stages of the disease, matrix metalloproteinases derived from macrophages or smooth-muscle cells themselves may contribute to weakening of the fibrous cap in the vulnerable shoulder area, promoting plaque rupture and occlusive thrombosis, culminating in the dramatic clinical manifestations of atherosclerosis, including myocardial infarction and stroke. Thus, cytokines can influence multiple aspects of atherogenesis and provide new and interesting targets for therapeutic intervention.
 ...
PMID:Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. 869 71

The original notion that the brain represented an "immune-privileged" organ lacking the capability to produce an inflammatory response to an injury, would appear no longer tenable. Indeed, accumulating evidence during the last decade has shown that the CNS can mount a well-defined inflammatory response to a variety of insults including trauma, ischemia, transplantation, viral infections, toxins as well as neurodegenerative processes. Many aspects of this centrally-derived inflammatory response parallel, to some extent, the nature of such a reaction in the periphery. Through the recent application of molecular biological techniques, new concepts are rapidly emerging as to the molecular mechanisms associated with the development of brain injury. In particular, the importance of cytokines, especially TNF alpha and IL-1 beta, as well as adhesion molecules, has been emphasized in the propagation and maintenance of a CNS inflammatory response. This review will summarize recent observations as to the involvement of these inflammatory mediators in CNS injury and lay claim to the possibility that inhibitors of peripheral inflammation may also be of benefit in treating CNS injuries such as stroke, head trauma, Alzheimer's disease and multiple sclerosis.
 ...
PMID:The role of inflammation and cytokines in brain injury. 888 Jul 34

It is our central hypothesis that periodontal diseases, which are chronic Gram-negative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL-1 beta, PGE2, and TNF-alpha) which serve to initiate and exacerbate atherogenesis and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow-up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease.
 ...
PMID:Periodontal disease and cardiovascular disease. 891 Aug 31

A rapidly expanding body of data provides support for the hypothesis that pro-inflammatory cytokines including interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) are expressed acutely in injured brain and contribute to progressive neuronal damage. Little is known about the pathogenetic role of these cytokines in perinatal brain injury. Recent experimental studies have incorporated two closely related in vivo perinatal rodent brain injury models to evaluate the role(s) of pro-inflammatory cytokines in the progression of neuronal injury: a perinatal stroke model, elicited by unilateral carotid artery ligation and subsequent timed exposure to 8% oxygen in 7-day-old rats, and a model of excitotoxic injury, elicited by stereotactic intra-cerebral injection of the selective excitatory amino acid agonist NMDA. Each of these lesioning methods results in reproducible, quantifiable focal forebrain injury at this developmental stage. Acute brain injury, evoked by cerebral hypoxia-ischemia or excitotoxin lesioning, results in transient marked increases in expression of IL-1 beta, and TNF-alpha mRNA in brain regions susceptible to irreversible injury, and there is evidence that pharmacological antagonism of IL-1 receptors can attenuate injury in both models. Recent studies also suggest that complementary strategies, based on pharmacological antagonism of platelet activating factor and on neutrophil depletion can also limit the extent of irreversible injury. In summary, current data suggest that pro-inflammatory cytokines contribute to the progression of perinatal brain injury, and that these mediators are important targets for neuroprotective interventions in the acute post-injury period.
 ...
PMID:Cytokines and perinatal brain injury. 910 51

Cerebrospinal fluid (CSF) and serum samples of 20 young adults (mean age 41 +/- 3.4 yr) with a first episode of stroke were tested for interleukin-2 (IL-2), soluble interleukin-2 receptor (SIL-2R), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) levels. The results were compared to 20 patients who had neurological symptoms without evidence of a neurological disease. Three subgroups were formed according to the aetiological source of the stroke, determined by the neurological examination and evaluation. In 13 patients, the presence of atheromatous carotid plaque or cardiac disease was found. In five of the patients, stroke was the presenting symptom of systemic lupus erythematosus (SLE), which developed during the follow-up period. In two patients, no obvious aetiology could be demonstrated. The SIL-2R level was significantly higher in the CSF of patients who later developed definite SLE (P = 0.001). Other CSF interleukins and all serum interleukin levels were not significantly different in any of the groups. No correlation between albumin quotient and CSF SIL-2R was found. The SIL-2R level in the CSF may be used as a diagnostic tool to differentiate immunologically mediated vascular processes in the CNS from stroke of other origin.
 ...
PMID:Cerebrospinal fluid soluble interleukin-2 receptor in cerebral lupus. 913 27

Secondary ischemic brain injury has been shown to develop as a consequence of inflammation and vasogenic brain edema. In this study we show that inflammatory cytokines and simulated in vitro ischemia stimulate the surface expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (E-selectin) in human cerebromicrovascular endothelial cells (HCEC) in culture. The levels of all three adhesion molecules were dramatically (3 to 10-fold) up-regulated by 4-24 hour exposure to the inflammatory cytokines. IL-1 beta (10-200 u/ml) or TNF alpha (50 200 u/ml), and by a 4 hour exposure to "simulated" in vitro ischemia, as determined by immunocytochemistry and ELISA. Following 24 hours of subsequent reperfusion, the expression of ICAM-1 and VCAM-1 was maintained at ischemia-induced levels, whereas E-selectin was no longer detectable. Both the cytokine- and ischemia-induced up-regulation of adhesion molecules were completely abolished by the transcriptional inhibitor, actinomycin D (10 micrograms/ml), and inhibited by the cycloxygenase (COX) inhibitor, indomethacin (300 microM). These findings implicate HCEC in the processes of leukocyte adhesion and recruitment in the brain during stroke in vivo.
 ...
PMID:Increase in surface expression of ICAM-1, VCAM-1 and E-selectin in human cerebromicrovascular endothelial cells subjected to ischemia-like insults. 941 64


1 2 3 4 Next >>