Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate some aspects of blood coagulation and of platelet function in cerebral ischemia, 18 healthy subjects, 24 patients with previous cerebral infarction and 12 patients with transient ischemic attacks were studied. All patients were in a non-active state of the illness. In all subjects, platelet count, prothrombin time, activated partial thromboplastin time and determination of the fibrinogen concentration were performed as routine. All subjects were tested for platelet adhesiveness, circulating platelet aggregates, factor VIII coagulant (VIII C), factor VIII-related von Willebrand factor (VII RWF), factor VIII-related antigen (VII RAg), antithrombin III (AT III) concentration and activity and euglobulin clot lysis time. No significant difference between patients and controls was found in routine tests, platelet function, AT III concentration or activity. Plasma levels of VIII C, VIII RWF, VIII RAg were significantly increased in both patient groups. The VIII RAg/VIII C ratio was significantly increased only in patients with previous cerebral infarction. Euglobulin clot lysis time was significantly increased in both patient groups.
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PMID:Evaluation of some coagulation parameters in cerebral ischemia. 685 12

The expression and localization of P- and E-selectins in rat brain (n=126) were examined using immunohistochemical techniques at various time points after induction of middle cerebral artery (MCA) occlusion in the suture, thrombotic and embolic models of stroke. Expression of P- or E-selectin was not observed in brain tissue of sham operated control rats (n=9). P-selectin immunoreactivity was detected as early as 15 min and decreased to control level at 1 h after the onset of the MCA occlusion in all three models. P-selectin then slightly increased at 2 h and peaked at 6 h after MCA occlusion. E-selectin immunoreactivity was first observed at 2 h and peaked at 6 h and 12 h of after MCA occlusion in all three models. P- and E-selectin immunoreactivity was colocalized with von Willebrand factor immunoreactive microvessels. 90.4+/-2.0% of all vessels expressing P-selectin immunoreactivity were 7.5 to 30.0 micron in diameter; 3.6+/-1.4% were contained in vessels smaller than 7.5 micron, and 6.0+/-1.8% were localized in vessels greater than 30.0 micron in diameter. The percent distribution of E-selectin immunoreactive vessels were 75.9+/-2.1% in vessels 7.5 to 30.0 micron in diameter; 23.6+/-2.2% were in vessels smaller than 7.5 micron, and 0.6+/-0.4% were localized in vessels greater than 30.0 micron in diameter. These findings indicate that the temporal profiles of P- and E-selectin expression are independent of these models of MCA occlusion and are consistent with the time course of selectin mediated leukocyte infiltration after focal cerebral ischemia in the rat.
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PMID:The expression of P- and E-selectins in three models of middle cerebral artery occlusion. 951 15

Abnormalities of coagulation and fibrinolysis may play an important role in the pathogenesis of ischaemic stroke and vascular dementia. We aimed to determine whether haemostatic function is altered in acute recent-onset or chronic ischaemic cerebrovascular disease. We studied consecutive patients with ischaemic stroke (n = 74) and vascular dementia (n = 42) compared with healthy controls (n = 40) in a case-control study. The ischaemic stroke group was assessed twice, 3-10 days after the acute stroke and at 1-3 months. Fibrinogen, fibrin D-dimer (marker of fibrin turnover) and von Willebrand factor (vWF) (marker of endothelial disturbance) were elevated acutely (P < 0.0001) and in the convalescent phase after ischaemic stroke (P < 0.0001, P < 0.0001, and P < 0.01 respectively, compared with controls). Similar results were seen in the vascular dementia group. Stepwise multivariate regression analyses showed that cerebrovascular disease correlated independently with fibrinogen (P < 0.001) and fibrin D-dimer levels (P < 0.001), while vWF correlated independently with electrocardiograph evidence of ischaemic heart disease (P = 0.004). Changes between acute and convalescent phases in ischaemic stroke were slightly inconsistent. However, in the acute stage there were tendencies for fibrinogen, D-dimer and vWF to be increased, and factor VIII was significantly higher. Abnormalities of haemostasis, including increased fibrin turnover and endothelial disturbance, are found in both acute and chronic cerebral ischaemia. Many of these patients have co-existent ischaemic heart disease and this may contribute to some of these changes. Acute ischaemic stroke is associated with transient changes in haemostatic factors; however, most abnormalities persist into the convalescent phase, and are also demonstrable in subjects with vascular dementia.
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PMID:Haemostasis in ischaemic stroke and vascular dementia. 1173 65

We investigated whether circulating endothelial progenitor cells contribute to neovascularization after stroke. Donor bone marrow cells obtained from transgenic mice constitutively expressing beta-galactosidase transcriptionally regulated by an endothelial-specific promoter, Tie2, were injected into adult mice. Focal cerebral ischemia was induced by embolic middle cerebral artery (MCA) occlusion and changes of cerebral blood flow (CBF) were measured by perfusion-weighted magnetic resonance imaging (MRI). Laser scanning confocal microscopy (LSCM), immunohistochemistry and X-gal staining were performed. Perfusion-weighted MRI demonstrated increases in CBF around the boundary of an infarct area 1 month after ischemia. Morphological and 3-dimensional image analyses revealed enlarged and thin-walled blood vessels with sprouting or intussusception at the boundary of the ischemic lesion, which closely corresponded to elevated CBF areas detected on perfusion-weighted MRI, indicating the presence of neovascularization. X-gal and double immunostaining demonstrated that Tie2-lacZ-positive cells incorporated into sites of neovascularization at the border of the infarct, and these cells exhibited an endothelial antigenic marker (von Willebrand factor). In addition, bone marrow recipient mice without ischemia showed incorporation of Tie2-lacZ-expressing cells into vessels of the choroid plexus. These data suggest that formation of new blood vessels in the adult brain after stroke is not restricted to angiogenesis but also involves vasculogenesis and that circulating endothelial progenitor cells from bone marrow contribute to the vascular substructure of the choroid plexus.
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PMID:Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. 1186 16

We report a patient with relapsing hereditary hemolytic uremic syndrome (HUS) that began in the neonatal period with life-threatening jaundice and hemolytic anemia. He progressed to end-stage renal failure at 14 years of age and had a cerebrovascular accident while on dialysis. The cause of HUS was a constitutional deficiency in the von Willebrand factor cleaving protease. Hematological features of HUS significantly improved following bilateral nephrectomy. After renal transplantation, he had an early recurrence of HUS associated with two episodes of retinal and cerebral ischemia. Long-term treatment with fresh-frozen plasma exchanges prevented recurrence of HUS, cerebrovascular attacks, and early loss of the graft.
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PMID:Plasma therapy in von Willebrand factor protease deficiency. 1237 19

Much attention has recently been focused on the interaction between unusually large von Willebrand factor multimers (UL-VWFM) and platelets under high shear stress in pathological thrombus formation. The antiplatelet drugs acetylsalicylic acid (aspirin) and a thienopyridine derivative (ticlopidine) are commonly used to treat cerebral ischemia but exert different effects on high-shear-stress-induced platelet aggregation (H-SIPA) in the plasma. To examine the effects of these drugs in the absence of plasma factors, we studied H-SIPA using washed platelets (WPs) and purified UL-VWFM. WPs were prepared from the blood of 9 aspirin-treated and 11 ticlopidine-treated patients with cerebral ischemia, and H-SIPA in the presence of UL-VWFM was measured using a cone plate aggregometer. Plasma levels of VWF antigen with its multimer analysis, ristocetin cofactor and VWF-cleaving protease (ADAMTS13) activity were also measured. Forty-six healthy volunteers from 2 age groups, 20-40 years (n=20) and 41-60 years old (n=26), were also tested as controls. H-SIPA was significantly inhibited for ticlopidine-treated platelets, but it was observed to a lesser extent for aspirin-treated platelets. For both groups, no difference in the plasma levels of VWF antigen, ristocetin cofactor and ADAMTS13 activity was noted. All patients possessed UL-VWFM, and it was detected in healthy volunteers with increasing frequency with increasing age. Under plasma-free conditions, platelets from aspirin-treated patients exhibit marginal but significant inhibition of H-SIPA. Furthermore, the presence of UL-VWFM in the plasma of patients and normal volunteers is directly related to their age rather than being a consequence of underlying disease.
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PMID:Platelets treated with ticlopidine are less reactive to unusually large von Willebrand factor multimers than are those treated with aspirin under high shear stress. 1629 84

Although stem cell-based treatments for stroke and other neurodegenerative diseases have advanced rapidly, there are still few clinical treatments available. In this study, rats receiving intracerebral peripheral blood hematopoietic stem cell (CD34+) (PBSC) transplantation showed much more improvement in neurological function after chronic cerebral ischemia in comparison with vehicle-treated control rats. Using laser-scanning confocal microscopy, implanted PBSCs were seen to differentiate into glial cells [GFAP+ (glial fibrillary acidic protein-positive)], neurons [Nestin+, MAP-2+ (microtubule-associated protein 2-positive), Neu-N+ (neuronal nuclear antigen-positive)], and vascular endothelial cells [vWF+ (von Willebrand factor-positive)], thereby enhancing neuroplastic effects in the ischemic brain. Cortical neuronal activity, as evaluated by 1H-MRS (proton magnetic resonance spectroscopy), also increased considerably in PBSC-treated rats compared with a vehicle-treated control group. In addition, PBSC implantation promoted the formation of new vessels, thereby increasing the local cortical blood flow in the ischemic hemisphere. These observations may be explained by the involvement of stem cell-derived macrophage/microglial cells, and beta1 integrin expression, which might enhance this angiogenic architecture over the ischemic brain. Furthermore, quantitative reverse transcription-PCR analysis showed significantly increased modulation of neurotrophic factor expression in the ischemic hemisphere of the PBSC-transplanted rats compared with vehicle-treated control rats. Thus, intracerebral PBSC transplantation might have potential as a therapeutic strategy for treating cerebrovascular diseases.
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PMID:Intracerebral peripheral blood stem cell (CD34+) implantation induces neuroplasticity by enhancing beta1 integrin-mediated angiogenesis in chronic stroke rats. 1657 51

Microcirculatory disturbances contribute to the expansion of infarct lesions after focal cerebral ischemia. Recently, it was shown that Rho-kinase involves in endothelial dysfunction via down-regulation of endothelial nitric oxide synthase function in a rodent stroke model. However, it is not clear whether endothelial Rho-kinase is activated in vivo or Rho-kinase activation contributes to microcirculatory disturbances after cerebral ischemia. In this study, we assessed the temporal and spatial profiles of Rho-kianse activity and the effect of the Rho-kinase inhibitor fasudil on microcirculatory disturbances in the focal brain ischemia. Rho-kinase activation was evaluated by analyzing the phosphorylation of adducin, a substrate of Rho-kinase, by immunohistochemistry. Staining for p-adducin was found in endothelia in the ischemic area 6 hr after induction of ischemia. Microcirculatory disturbances and increased endothelial cell staining for von Willebrand factor (vWF) were observed in the same area. Postischemic treatment with fasudil suppressed endothelial Rho-kinase activation, preserved microcirculation, and inhibited endothelial cell vWF staining. These effects resulted in inhibition of infarct expansion and improvement of neurologic deficits. These findings indicate that Rho-kinase is activated in the endothelial cells and contributes to microcirculatory disturbances in cerebral ischemia. The vascular protective effect of Rho-kinase inhibitors may be useful in the treatment of the acute phase of ischemic stroke.
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PMID:Rho-kinase activation in endothelial cells contributes to expansion of infarction after focal cerebral ischemia. 1752 23

We recently demonstrated that blockade of the platelet adhesion receptor glycoprotein (GP) Ibalpha protects mice from ischemic stroke. Although von Willebrand factor (VWF) is the major ligand for GPIbalpha, GPIbalpha can engage other counterreceptors on endothelial cells, platelets, and leukocytes (eg, Mac-1 or P-selectin) potentially involved in stroke outcome. To further analyze whether VWF is of particular relevance for stroke development, VWF(-/-) mice underwent 60 minutes of middle cerebral artery occlusion. After 24 hours, VWF(-/-) mice had significantly smaller infarctions (P< .05) and less severe neurologic deficits (P< .01) compared with controls. This effect was sustained after 1 week, and intracranial bleeding was absent in VWF(-/-) mice as revealed by serial magnetic resonance imaging. Hydrodynamic injection of a VWF-encoding plasmid restored the susceptibility for stroke in VWF(-/-) mice. This study indicates that VWF is critically involved in cerebral ischemia. Hence, targeted inhibition of the GPIbalpha-VWF pathway might become a promising therapeutic option.
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PMID:Deficiency of von Willebrand factor protects mice from ischemic stroke. 1918 8

Previous studies have shown that Qing Kai Ling, a traditional Chinese medicine, was able to effectively prevent the inflammation from cerebral ischemia (Chen et al., 2002). The cholalic acid and hyodeoxycholalic acid (cholalic acid mixture) was major active components in Qing Kai Ling. To study the effects of cholalic acid mixture on the damage cascade of cerebral ischemia, rat model of focal cerebral ischemia was established by permanent occlusion of left middle cerebral artery. We found that the administration of cholalic acid mixture could reduce the ischemic infarct size after 24 h of ischemia, and cholalic acid mixture could be detected in cerebrospinal fluid after 2h of administration. We also found that the concentrations of tumor necrosis factor-alpha and interlukin-1beta in rat brain were significantly lower when compared to the untreated animals after 12 h and 24 h of ischemia. The concentrations of von Willebrand factor and neuron specific enolase in the plasma were remarkably decreased in cholalic acid mixture treated animals than in the untreated ones after 12h of ischemia. Our results suggested that cholalic acid mixture is able to decrease the expression of inflammation factors including tumor necrosis factor-alpha and interlukin-1beta after focal cerebral ischemia.
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PMID:The inhibitory effects of cholalic acid and hyodeoxycholalic acid on the expression of TNFalpha and IL-1beta after cerebral ischemia in rats. 1918 78


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