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Background/aims: To measure the risk of vascular event occurrence among postischemic stroke patients in mainland China., Methods: In this multicenter prospective stroke registry study, we enrolled 1,951 patients diagnosed with acute ischemic stroke. Demographic data, prestroke risk factors, severity of neurological deficits and disability graded on the National Institutes of Health Stroke Scale (NIHSS), and modified Rankin Scale scores of each patient were measured and recorded. Patients were followed up regularly for 12 months after recruitment. Clinical endpoints were defined as occurrence of vascular events or death., Results: We detected 103 cases with nonfatal vascular events and 27 cases that died of vascular events. Cumulative incidences of total vascular events, cerebrovascular events, and coronary artery diseases were 7.2, 5.0, and 1.8%, respectively, at 12 months after the initial ischemic stroke. Concomitant atherosclerotic-thrombotic diseases (HR, 1.68; 95% CI, 1.14-2.43) and baseline NIHSS (HR, 1.07; 95% CI, 1.03-1.11) were found to be the best predictors for further occurrence of a vascular event. Antiplatelet therapy (HR, 0.52; 95% CI, 0.35-0.77) is associated with a lower risk of further vascular events., Conclusion: Our study provided valuable data on prognosis of acute ischemic stroke in Chinese patients., (Copyright 2009 S. Karger AG, Basel.)

Background: Evidence of the beneficial effects of antiplatelet therapy after ischemic stroke is currently lacking in China., Methods and Results: Demographic data, pre-stroke risk factors, severity of neurological deficit, and disability graded by the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) of 1,951 patients were measured and recorded at baseline. Regular follow-up by interview was performed for 12 months post-recruitment. The all-cause mortality was 1.88 per 100 person-years during the follow-up period. Recurrent fatal and nonfatal cerebrovascular events occurred in 90 patients, accounting for 4.24 per 100 person-years of cumulative incidence. After adjustment by other variables, antiplatelet therapy was identified as an independent protective predictor of all-cause death (hazard ratio (HR) 0.42; 95% confidence interval (CI) 0.21-0.86; P=0.017) and recurrent cerebrovascular events (HR 0.58; 95%CI 0.36-0.92; P=0.021). Among survivors, antiplatelet therapy was also an independent predictor for improvement in the NIHSS (HR 1.27; 95%CI 1.07-1.51; P=0.006) and the MRS (HR 1.25; 95%CI 1.02-1.52; P=0.031)., Conclusions: The data from this multicenter, prospective study confirmed the association between antiplatelet therapy and decreased risk of all-cause mortality and recurrent cerebrovascular events after ischemic stroke in Chinese patients.

In several experimental studies of cerebral ischemia, G-CSF exerts neuroprotective effects through different mechanisms, including mobilization of hematopoietic stem cells, anti-apoptosis, neuronal differentiation, angiogenesis and anti-inflammation. Hence, G-CSF not only inhibits neuron death, but also generates "new" neural tissue formation. A small pilot trial reports on the safety and feasibility of G-CSF therapy in stroke patients. According to this evidence, we can speculate that G-CSF, being used either alone or in combination with another agent, should be an effective strategy in the treatment of cerebral ischemia.

Calcium toxicity remains the central focus of ischemic brain injury. Calcium channel antagonists have been reported to be neuroprotective in ischemic animal models but have failed in clinical trials. Rather than block the calcium channels, calbindin proteins can buffer excessive intracellular Ca2+, and as a result, maintain the calcium homeostasis. In the present study, we investigated the effect of calbindin D 28k (CaBD) in ischemic brain using the novel technique protein transduction domain (PTD)-mediated protein transduction. We generated PTD-CaBD in Escherichia coli, tested its biologic activity in N-methyl-D-aspartate (NMDA)- and oxygen-glucose deprivation (OGD)-induced hippocampal injury models, and examined the protection of the fusion protein using a rat brain focal ischemia model. Infarct volume was determined using 2,3,5-triphenyl-tetrazolium chloride staining; neuronal injury was examined using terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining and cleaved caspase-3 assay. The results showed that the PTD-CaBD was efficiently delivered into Cos7 cells, hippocampal slice cells, and brain tissue. Pretreatment with PTD-CaBD decreased intracellular free calcium concentration and reduced cell death in NMDA- or OGD-exposed hippocampal slices (P<0.05). Intraperitoneal administration of PTD-CaBD before transient middle cerebral artery occlusion decreased brain infarct volume (280+/-47 versus 166+/-70 mm3, P<0.05), and improved neurologic outcomes compared with the control. Further studies showed that, compared with the control animals, PTD-CaBD decreased TUNEL (58%+/-7% versus 29%+/-3%, P<0.05)- and cleaved caspase-3 (62+/-4/field versus 31+/-6/field, P<0.05)-positive cells in the ischemic boundary zone. These results indicate that systemic administration of PTD-CaBD could attenuate ischemic brain injury, suggesting that PTD-mediated protein transduction might provide a promising and effective approach for the therapies of brain diseases, including cerebral ischemia.

In several experimental studies of cerebral ischaemia, G-CSF (granulocyte colony-stimulating factor) exerted neuroprotective effects through different mechanisms, including mobilization of haemopoietic stem cells, anti-apoptosis, neuronal differentiation, angiogenesis and anti-inflammation. Hence, G-CSF not only inhibits neuron death, but also generates 'new' neural tissue formation. A small pilot trial reports on the safety and feasibility of G-CSF therapy in stroke patients. According to this evidence, we can speculate that G-CSF, being used either alone or in combination with another agent, should have a dual activity beneficial both to acute neuronal protection and long-term plasticity after cerebral ischaemia, thus proposing that G-CSF is an ideal new drug for stroke and neurodegenerative diseases.

Anti-apoptotic treatment is a promising strategy for neuroprotection against various brain injuries resulting from ischemia or neuron degeneration. X-linked inhibitor of apoptosis protein (XIAP) is regarded as the most effective apoptosis inhibitor, in which C-terminal structure BIR3-RING mainly inhibits caspase-9-dependent apoptosis. In the present study, we fused XIAP (BIR3-RING) to the protein transduction domain (PTD) of antennapedia homeodomain of Drosophila (Antp HD), and then used the oxygen glucose deprivation (OGD)-induced hippocampal slices injury in vitro, and the rat transient middle cerebral artery ischemia (tMCAO) models in vivo, to explore the anti-apoptotic effect of this recombinant protein. The results showed that the PTD could efficiently mediate the transduction of BIR3-RING into the hippocampal slices and rat brains. PTD-BIR3-RING could decrease OGD-induced cell death in brain slices (p < 0.05). Intraperitoneal injection of PTD-BIR3-RING could attenuate terminal deoynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) positive cells and decrease cleaved caspase-3 in the ischemic bounder zone compared with the control animals (p < 0.05). Further studies showed that ischemia-induced neurological outcomes were improved in rats with PTD-BIR3-RING treatment (p < 0.05). These results demonstrate that PTD-BIR3-RING could attenuate cell death in OGD hippocampal slices and decrease cell apoptosis in tMCAO brains through inhibiting of caspase-3 cleavage, suggesting that PTD-mediated protein transduction provides a novel and effective approach for the therapies of brain diseases such as cerebral ischemia.

Objective: To investigate whether the extent of white matter lesions (WML) on fluid attenuated inversion recovery (FLAIR) MRI sequences is an independent risk factor for recurrent stroke, and to document the pattern of acute cerebral infarcts using diffusion weighted imaging (DWI) in patients with different severities of WML., Methods: In a prospective cohort study, 228 consecutive stroke patients were studied between 1999 and 2001 in a community hospital. The severity of WML was graded as 0 (no WML), 1 (mild), 2 (moderate), or 3 (severe) according to the FLAIR appearances. DWI was used to document the location and size of the infarct., Results: 31 patients had grade 0 WML, 69 had grade 1, 59 had grade 2, and 69 had grade 3. Age was independently associated with WML on logistic regression analysis (p = 0.0001). Acute cerebral infarcts in deep white matter were correlated with increasing severity of WML. On a median follow up of 23.0 months, life table analysis showed that recurrent stroke was related to the severity of WML (recurrence rate 7.8% in grade 0, 9.3% in grade 1, 17.7% in grade 2, 43.7% in grade 3; p = 0.0001). Survival was reduced in patients with severe WML (p = 0.0068). A Cox proportional hazards model showed WML to be predictive of recurrent stroke (p = 0.000, hazard ratio = 4.177 (95% confidence interval, 2.038 to 8.564)) and also for survival (p = 0.040, hazard ratio = 2.021 (1.032 to 3.960))., Conclusions: Patients with severe leukoaraiosis have increased risk of deep subcortical stroke and a higher risk of recurrent stroke.

The purpose of this study is to discuss an important component-arachidonic acid (AA) cascade of inflammatory reaction in diabetic rats with cerebral ischemia. Using the model of middle cerebral artery occlusion (MCAO), we have compared the expression of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), and measured the levels of their products prostaglandin E2 (PGE(2)) and cysteine-containing leukotrienes (cys-LTs) after different reperfusion periods in diabetic and normal rats. Cerebral ischemia-reperfusion was accompanied by increased expression of COX-2 and release of PGE(2), peaking at 12 h after reperfusion. The expression of COX-2 was maintained at a high level until 24 h after reperfusion, while the levels of PGE(2) were declined rapidly to baseline. The expression of 5-LOX and levels of cys-LTs reached a peak at 6 and 12 h after reperfusion, respectively, and was returned to baseline at 24 h after reperfusion. Compared with normal rats, the expression of COX-2 and 5-LOX as well as release of PGE(2) and cys-LTs was elevated in the brains of diabetic rats, revealing a possible mechanism for hyperglycemia-mediated aggravation of cerebral ischemic injury. A reduction of arachidonic acid metabolites mediated by inhibitors of its metabolites could be helpful in preventing ischemic brain injury in diabetic rats.