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)

Variability in microvessel changes of blood vessel density has prompted us to undertake quantitative morphometric studies of infarcted areas in human brain. In the initial study, brains were obtained at autopsy from 10 patients (ages 45-85). Samples were collected from infarcted hemisphere and controls from the contralateral hemisphere. Formalin fixed, paraffin embedded and thereafter routinely processed sections were stained after Pickworth and with HE. Altogether 6,520 microvessels, representing 10,801 microscopic fields were counted. The Wilcoxon Range test was used for statistical analysis. In 9 of 10 patients in infarcted brain hemispheres, there was a marked increase in microvessel density (p < 0.01), when compared with contralateral brain hemisphere. In addition, a positive correlation was also found between the time of survival and both total density and density of non-perfused blood vessels. To gain a deep insight into the enhanced activity of microvessels, immunocytochemical studies were performed, which have shown, that the vascular endothelial cells in infarcted brain were reactive to two monoclonal antibodies, one, E-9, directed against an activation/proliferation associated endothelial cell specific protein and the other recognizing adhesion molecule VCAM-1. Pan-endothelial Mab PECAM/CD31 was used in those studies for controls and confirmed the obtained results. Our findings strongly support the concept of angiogenesis in the infarcted area. If correlated with morphometric results, it may indicate an important role of microvessels in pathobiology of ischemic stroke.
 ...
PMID:Some remarks on the growth-rate and angiogenesis of microvessels in ischemic stroke. Morphometric and immunocytochemical studies. 750 94

Various molecules expressed on the surface of platelets have been shown to mediate the protective or deleterious role of these cells in immuno-inflammatory mechanisms. Increasing evidence points to the involvement of the cell adhesion molecules, gpIIb-IIIa, P-selectin, CD31, LFA-1, and CD36 in the interaction between platelets and endothelial cells as well as other cell types. The possible role of these molecules in the ability of platelets to support endothelium and to protect against tumour necrosis factor mediated cytolysis or parasitic invasion are reviewed. The involvement of platelets as effectors of tissue damage in cerebral malaria, lipopolysaccharide induced pathology, and pulmonary fibrosis is also discussed. This has then been extended to include the intercellular mechanisms underpinning their pathogenic role in metastasis, transplant rejection, stroke, brain hypoxia, and related conditions. A better understanding of the complex regulation and hierarchical organisation of these various platelet adhesion molecules may prove useful in the development of new approaches to the treatment of such diseases.
 ...
PMID:Role of platelet adhesion in homeostasis and immunopathology. 935 Mar

We studied the effect of topically applied phenytoin on the healing of a decubitus ulcer in the sacral region of an immobile patient with stroke. Another similar, but smaller, ulcer was treated with conventional treatment only and served as a control. The ulcers were measured once a week and biopsies were taken from the margins before, 1 week and 2 weeks after commencing treatment with phenytoin. Clinically, phenytoin substantially accelerated the rate of healing. Microscopic examination of the biopsies showed increased lymphocytic infiltration of the phenytoin-treated lesion. Anti-CD31 immunohistochemistry revealed dense CD31+ lymphocytic infiltration and increased angiogenesis only in the phenytoin-treated lesion. Our findings suggest that phenytoin enhances wound healing by stimulating lymphocytic chemotaxis and up-regulation of angiogenesis.
 ...
PMID:Phenytoin-induced lymphocytic chemotaxis, angiogenesis and accelerated healing of decubitus ulcer in a patient with stroke. 1508 24

Multipotent adult progenitor cells, which can differentiate into mesenchymal cells as well as cells with visceral mesoderm, neuroectoderm and endoderm characteristics, have been identified in the bone marrow. We examined whether bone marrow-derived cells can differentiate into the major cell types in the brain, including neuron, astrocyte, microglia and endothelium, in response to cerebral focal ischemia under treatment with cytokines. Bone marrow cells, which were sampled from green fluorescent protein (GFP)-expressing transgenic mice, were transplanted into irradiated female C57 Black/6 mice. Two months later, the recipient mice received permanent occlusion of the middle cerebral artery, then were treated with cytokines. One month after the occlusion, GFP-expressing cells, considered to be bone marrow-derived, were identified as neurons, endothelial cells, microglias and macrophages by means of NeuN, CD31, major histocompatibility complex class I antigen, and CD45 labeling, respectively, observed with confocal microscopy. These results indicate that the bone marrow-derived cells are, at least in part, a source of neurons as well as endothelial cells generated in response to cerebral infarction, in the presence of cytokines. This finding may suggest a new therapeutic strategy to enhance neuronal and vascular regeneration after stroke in the clinical field.
 ...
PMID:[Differentiation of adult bone marrow cells into neurons and endothelial cells in rat brain after stroke in the presence of cytokines]. 1515 77

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a 130-kDa protein, which plays a significant role in the adhesion cascade. It is therefore involved in leucocyte endothelium interaction and in leucocyte transendothelial migration during inflammation. As neuroinflammation and subsequent blood brain barrier disruption are integral processes in many neurological disorders, PECAM-1 and its soluble form (sPECAM-1) have been investigated in a number of conditions, rising hopes as a potential marker of disease activity, a possible target in treatment and a prognostic factor. It has been shown that serum and CSF levels of PECAM-1 and sPECAM-1 are increased in patients in active stages of multiple sclerosis. Similarly, they rise in individuals after ischaemic stroke. PECAM-1 has also been shown to be involved in the pathogenesis of Abeta-related cerebral vascular disorders, such as Alzheimer disease. It participates in the pathomechanism of paraneoplastic neurological disorders and in neuroinflammation in NeuroAIDS. A number of experiments on animal models were carried out in order to investigate PECAM-1 role in the above-mentioned conditions and more, including brain trauma and nerve root injury. In this review most recent investigations on PECAM-1 biology and its role in neuroinflammation have been described and discussed from a multidisciplinary point of view.
 ...
PMID:PECAM-1, a key player in neuroinflammation. 1711 9

Fabry disease is an inborn error of glycosphingolipid catabolism resulting from a deficiency of lysosomal enzyme alpha-galactosidase A. The major clinical manifestations of the disease, such as stroke, cardiac dysfunction, and renal impairment, are thought to be caused by vasculopathy due to progressive accumulation of globotriaosylceramide in vascular endothelial cells. The pathogenesis of the vasculopathy has not been elucidated. Since in vitro studies using primary endothelial cells are hampered by the limited lifespan of these cells, the availability of cultured endothelial cells with an extended lifespan is critical for the study of the vasculopathy of Fabry disease. We therefore generated an endothelial cell line from a Fabry hemizygote by introduction of human telomerase reverse transcriptase gene. The cell line has markedly extended lifespan compared to parental primary cells. The cells stably express many key markers of endothelial cells such as von Willebrand factor, CD31, CD34, and endothelial nitric oxide synthase (eNOS) and retain functional characteristics such as uptake of acetylated low-density lipoprotein, responsiveness to angiogenic growth factors, up-regulation of eNOS production upon extracellular stimuli, and formation of tube-like structures on Matrigel basement membrane matrix. The cells show significantly reduced activity of alpha-galactosidase A compared with primary endothelial cells from normal individuals and accumulate globotriaosylceramide in lysosomes. This cell line will provide a useful in vitro model of Fabry disease and will facilitate systematic studies to investigate pathogenic mechanisms and explore new therapeutic approaches for Fabry disease.
 ...
PMID:Establishment and characterization of Fabry disease endothelial cells with an extended lifespan. 1764 84

Growth factors are currently evaluated as therapeutics in stroke and neurodegeneration. Besides direct neurotrophic effects, they promote proliferation, survival, and differentiation of both transplanted and endogenous neural precursor cells (NPCs). In the current study, we investigated whether NPCs expressing Vascular Endothelial Growth Factor VEGF-A165 are a useful vehicle for growth factor delivery after transplantation into the caudate putamen of the rat brain. We found an increased survival of adenovirally transfected NPCs after 11 days, but not after 24 hours or 4 days. Additional brain immunohistochemistry revealed increased expression of the endothelial cell marker PECAM-1 (CD31) after 24 hours, 4 day, and 11 days after transplantation. In conclusion, we show that the graft itself is a useful vehicle for growth factor delivery, promoting the survival of NPCs. Moreover, transplantation of VEGF-expressing NPCs supports angiogenesis in the brain, which may contribute to potential brain repair.
 ...
PMID:Transplantation of adult neural progenitor cells transfected with vascular endothelial growth factor rescues grafted cells in the rat brain. 1816 30

Developmental endothelial locus-1 (Del-1) is a novel angiomatrix protein that has been shown to stimulate a potent angiogenic response and promote functional recovery in hind-limb and cardiac ischemia in animal models; however, its impact on cerebral angiogenesis is unknown. In this study, we investigated whether Del-1 overexpression via gene transfer induces cerebral angiogenesis in a murine model, and examined Del-1 expression after ischemic stroke. Cerebral Del-1 overexpression was achieved with AAV (adeno-associated virus) transduction system via stereotactic injection. Control mice were injected with AAV-lacZ. Del-1 gene transduction led to a significant induction of cerebral angiogenesis compared to AAV-lacZ treatment at 4 weeks after gene transfer (Del-1: 97+/-7 vs lacZ: 64+/-28, vessels/field, p<0.05). Mice transduced with AAV-Del-1 showed significantly elevated vascular densities for up to 6 weeks after gene delivery. In addition, double immunofluorescent staining showed co-localization of endothelial cell marker CD31 with BrdU (specific marker for proliferating cells), indicating that Del-1 promoted endogenous endothelial cell proliferation and angiogenesis. Our immunohistochemical staining also showed that Del-1 expression was markedly up-regulated in the peri-infarct area at 3 days after permanent focal cerebral ischemia compared to the sham-operated non-ischemic control. Our data suggest that Del-1 may participate in modulating cerebral angiogenesis, and that gene transfer of Del-1 may provide a novel and potent means for stimulating cerebral angiogenesis.
 ...
PMID:Del-1 gene transfer induces cerebral angiogenesis in mice. 1853 62

Appropriate restoration of blood flow via angiogenesis is critical for the recovery from ischemic stroke. Previously, we reported that treatment with dl-3n-butylphthalide (NBP) increases the number of local potent cerebral microvessels. However, the underlying mechanism remained unclear. The present study was conducted to test whether NBP enhances post-ischemic cerebral angiogenesis via vascular endothelial growth factor (VEGF) and hypoxia induced factor-1 alpha (HIF-1 alpha). Stroke-prone renovascular hypertensive rats (RHRSP) were used to create middle cerebral artery occlusion (MCAO) model. NBP was given 80 mg/kg per d for 10 consecutive days, starting 12, 24, 48 and 72 h respectively after MCAO. Neurological function was assessed daily and infarct volume as well as the expressions of CD31, VEGF, HIF-1 alpha and bFGF was detected 13 days after MCAO. The administration of NBP starting within 24 h after MCAO enhanced recovery of neurobehavioral function, reduced infarct volume, increased the quantity of CD31 positive vessels, and up-regulated expressions of VEGF and HIF-1 alpha. These findings suggest that treatment with NBP within 24 h post-ischemic stroke rescues brain tissue by enhancing angiogenesis associated with up-regulation of VEGF and HIF-1 alpha expressions.
 ...
PMID:Enhanced angiogenesis with dl-3n-butylphthalide treatment after focal cerebral ischemia in RHRSP. 1952 55

Glial scarring is traditionally thought to be detrimental after stroke. But emerging studies now suggest that reactive astrocytes may also contribute to neurovascular remodeling. Here, we assessed the effects and mechanisms of metabolic inhibition of reactive astrocytes in a mouse model of stroke recovery. Five days after stroke onset, astrocytes were metabolically inhibited with fluorocitrate (FC, 1 nmol). Markers of reactive astrocytes (glial fibrillary acidic protein (GFAP), HMGB1), markers of neurovascular remodeling (CD31, synaptophysin, PSD95), and behavioral outcomes (neuroscore, rotarod latency) were quantified from 1 to 14 days. As expected, focal cerebral ischemia induced significant neurological deficits in mice. But over the course of 14 days after stroke onset, a steady improvement in neuroscore and rotarod latencies were observed as the mice spontaneously recovered. Reactive astrocytes coexpressing GFAP and HMGB1 increased in peri-infarct cortex from 1 to 14 days after cerebral ischemia in parallel with an increase in the neurovascular remodeling markers CD31, synaptophysin, and PSD95. Compared with stroke-only controls, FC-treated mice demonstrated a significant decrease in HMGB1-positive reactive astrocytes and neurovascular remodeling, as well as a corresponding worsening of behavioral recovery. Our results suggest that reactive astrocytes in peri-infarct cortex may promote neurovascular remodeling, and these glial responses may aid functional recovery after stroke.
 ...
PMID:Inhibition of reactive astrocytes with fluorocitrate retards neurovascular remodeling and recovery after focal cerebral ischemia in mice. 1999 16


1 2 3 4 5 6 Next >>