Flow cytometric analysis of reticulated platelets in patients with ischemic stroke

Reticulated platelets are newly formed platelets containing a residual amount of RNA, and percentage of reticulated platelets (%RP) has been shown to reflect platelet turnover. Recently, a new flow cytometric approach for analyzing %RP in patients with thrombocytopenic disorders has been reported. We measured %RP by flow cytometry using the fluorescent dye thiazole orange (TO) to evaluate platelet kinetics in patients with different clinical categories of ischemic stroke. Patients with ischemic stroke were categorized into lacunar (n=25), atherothrombotic (n=26) and cardioembolic stroke (n=17). %RP was significantly higher in patients with cardioembolic stroke than in controls (n=140). Stepwise multiple regression analysis also showed cardioembolic stroke (R(2)=0.14) to be significant independent predictors of %RP among stroke patients even after adjustment for other factors. We concluded that %RP is increased in patients with cardioembolic stroke, which may reflect increased platelet turnover as a consequence of platelet consumption during thrombogenesis.     

Serial measurement of surface expressions of CD63, P-selectin and CD40 ligand on platelets in atherosclerotic ischemic stroke. A possible role of CD40 ligand on platelets in atherosclerotic ischemic stroke

BACKGROUND: Platelet activation is a key step in the progression of atherosclerosis. The CD40 ligand (CD40L) on platelets may be a critical factor to develop the acute vascular events from atheroma. METHODS: To determine the role of CD40L on platelets in atherosclerotic ischemic stroke, we serially measured the expressions of CD63, P-selectin and CD40L on platelets in patients with atherosclerotic ischemic stroke (n = 25) and compared them with those in patients with asymptomatic carotid stenosis (n = 20) and in normal subjects (n = 24). RESULTS: The expressions of CD63 and P-selectin on platelets were significantly higher in patients with atherosclerotic ischemic stroke (n = 25) than in normal subjects (n = 24). The extents of surface expressions of CD63 and P-selectin on platelets showed no significant differences between atherosclerotic ischemic stroke and asymptomatic carotid stenosis. However, the CD40L expression on platelets was significantly higher in atherosclerotic ischemic stroke when compared to that in asymptomatic carotid stenosis. CONCLUSIONS: In our data, among the population with large artery atherosclerosis, the patients with symptomatic ischemic events showed a significantly elevated expression of CD40L on platelets compared to those without ischemic events. Therefore, the upregulation of CD40L on platelets may be a specific marker of platelet activation to provoke ischemic stroke from large artery atherosclerosis.     

Arterial ischemic stroke in an adolescent with presumed perinatal ischemic stroke

The risk of recurrent ischemic stroke after presumed perinatal stroke and the risk factors for such recurrence are rarely reported. Here, we present an adolescent with a history of presumed perinatal stroke who presented with arterial ischemic stroke recurrence at the age of 15 years. Hereditary thrombophilia screening performed at the time of his stroke recurrence demonstrated protein S deficiency. No evidence-based consensus guidelines on thrombophilia screening in children with presumed perinatal stroke exist, nor has the role of secondary prophylaxis been addressed. There is a risk of stroke recurrence after presumed perinatal stroke, and routine thrombophilia screening may identify those children who are at higher risk for recurrence and who might therefore benefit from secondary prophylaxis. Clear guidelines should be developed to standardize investigations and management of children with presumed perinatal ischemic stroke.     

Hyperhomocysteinemia in ischemic stroke

In the past decade, elevated levels of plasma homocysteine have emerged as a potential risk factor for vascular disease. Homocysteine is central in the metabolism of multiple vitamins, including cobalamin and folic acid. There are many reasons for elevated homocysteine levels, but folate deficiency is the most common, even in developed countries. Prospective studies correlating risk of heart disease and homocysteine have provided conflicting data. Data are stronger for the risk of cerebrovascular disease being related to high homocysteine concentrations. Therapy for most patients involves vitamin replacement. Early trial data indicate that lowering of homocysteine may reduce vascular complications.     

缺血性卒中后的神经炎性反应

神经炎性反应在缺血性卒中后的病理损伤中起重要作用。越来越多的证据表明,神经炎性反应是一把"双刃剑",在加重急性期卒中脑损伤的同时,亦可促进卒中后的神经修复。本文阐述了缺血性卒中后神经炎性反应的关键因素,如炎性细胞、炎性介质和黏附分子的变化,探讨了其可能的神经损伤及神经保护作用;同时,对缺血性卒中后神经炎性反应相关研究的进展及前景进行了综述。     

Pediatric ischemic stroke

Journal of Neurology -     

Genetics of ischemic stroke

Stroke is the third leading cause of death and a major cause of disability worldwide. Most cases of ischemic stroke are attributable to hypertension and other risk factors, but in over 20% of cases, the cause is unknown. Recent research has implicated some novel genes in the etiology of ischemic stroke, including genes for soluble epoxide hydrolase (sHE), 5-lipoxygenase activating protein (FLAP) and phosphodiesterase 4D (PDE4D). Moreover, thrombophilic states such as prothrombin G20210A mutation and factor V Leiden are now known to cause arterial stroke as well as venous thrombosis. Meanwhile, the recent availability of enzyme replacement therapy for Fabry disease and the proven benefits of regular blood transfusion in certain patients with sickle cell disease have greatly altered the outlook of these devastating inherited disorders. Thus, our understanding of the role of genetic factors in stroke raises the prospects for accurate assessment of future stroke risk among susceptible individuals, in whom early preventive measures may be life-saving. Further research into the genetics of stroke will clearly compliment ongoing national and international efforts to reduce the global burden of stroke.     

Targeting O-GlcNAcylation in ischemic stroke

Ischemic stroke is a common and often devastating disease that primarily affects the elderly. Treatment currently consists predominantly of acute thrombolysis a...     

Cell-based therapy in ischemic stroke

Cell-based therapy for stroke represents a third wave of therapeutics for stroke and one focused on restorative processes with a longer time window of opportunity than neuroprotective therapies. An early time window, within the first week after stroke, is an opportunity for intravenously delivered bone marrow and perinatally derived cells that can home to areas of tissue injury and target brain remodeling. Allogeneic cells will likely be the most scalable and commercially viable product. Later time windows, months after stroke, may be opportunities for intracerebral transplantation of neuronally differentiated cell types. An integrated approach of cell-based therapy with early-phase clinical trials and continued preclinical work with focus on mechanisms of action is needed.     

Antiedema therapy in ischemic stroke

Life-threatening, space-occupying brain edema occurs in up to 10% of patients with supratentorial infarcts and is traditionally associated with a high mortality rate of up to 80%. Management of these patients is currently being changed to an earlier and more aggressive treatment regimen. Early surgical decompression has recently been proven effective to reduce mortality and increase the number of patients with a favorable outcome in randomized controlled trials and is now the "antiedema" therapy of first choice for patients with large middle cerebral artery infarction aged 60 years or younger. Several medical treatment strategies have been proposed to control brain edema and reduce intracranial pressure, including different osmotherapeutics, hyperventilation, tromethamine, hypothermia, and barbiturate coma. None of these treatments is supported by level 1 evidence of efficacy in clinical trials, and some of them may even be detrimental. Preliminary results on hypothermia for space-occupying hemispheric infarction are encouraging, but far from definitive.     

Prothrombotic states in ischemic stroke

Ischemic stroke is a complex disease process consisting of multiple underlying mechanisms, including thromboembolic consequences of large arterial atherosclerotic disease. In addition to the traditional stroke risk factors, attention has also been focused on complex hemostatic functions, such as platelet aggregation, thrombin generation, and fibrinolysis. Information from prospective epidemilogic studies of hemostatic risk factors and ischemic stroke is incomplete and sometimes contradictory. There are fairly good data supporting an association between elevated fibrinogen and tissue plasminogen activator antigen and ischemic stroke. However, it is unknown if they are merely epiphenomena or pathogenic. The classic inherited risk factors for venous thromboembolic events (ie, antithrombin, protein C, and protein S deficiencies, and factor V Leiden and prothrombin G20210A polymorphisms) do not appear to be strong, independent risk factors in unselected stroke patients. Discovery of genetic polymorphisms in many hemostatic genes has stimulated searches for gene-disease associations, frequently before establishing that a polymorphism has an effect on protein expression or function. Future investigations into ischemic stroke risk factors should be prospective, enroll much larger numbers of subjects, rigorously classify strokes by subtype, and incorporate evolving molecular techniques to maximize collection of genetic information. This may lead to identification of unique gene-gene and gene-environmental interactions that may improve our understanding of the causes of ischemic strokes.     

Morbidity predictors in ischemic stroke

BACKGROUND: Although ischemic CVA is one of the leading causes for death and disability, parameters for predicting long-term outcome in such patients have not been clearly delineated, especially in the Indian context. METHODS: A prospective hospital-based study of 105 patients of ischemic stroke, focal neurological deficits and functional score was assessed and the C-reactive protein level (CRP) was measured. A follow-up was done at 5 days and at 6 months and outcome variable was the functional status at 6 months using Barthel Index of Activities of Daily Living. Accordingly, patients were grouped into 3 - Barthel Index < 41: Severely disabled, Barthel Index 41-60: Moderately disabled and Barthel Index > 60: Mildly disabled. RESULTS: At admission, if upper limb power was less than Medical Research Council (MRC) grade 4, or aphasia was present or CRP assay was positive, then at 6 months, these patients most likely belonged to the severely disabled group. If upper limb or lower limb power was greater than MRC grade 3 or there was no aphasia or conjugate gaze deviation or CRP assay was negative, these patients most likely belonged to the mildly disabled group at 6 months. Follow-up rate was 86%. CONCLUSION: Patients can be stratified according to the predicted prognosis. The treatment and rehabilitation can be properly planned and strictly adhered to in patients predicted to have worse prognosis.