Transitions of care for stroke and TIA.

PURPOSE: The purpose of this study was to identify elements of a stroke population that may affect transitions of care (TOC). DATA SOURCES: A retrospective analysis of the demographic characteristics of patients from an urban primary stroke center with an admitting diagnosis of transient ischemic attack, acute ischemic stroke, subarachnoid hemorrhage, or intracerebral hemorrhage was performed over an 8-month period (N = 276). A subset of this patient sample participated in a telephone survey 1 month after discharge. CONCLUSION: Hospital length of stay, age, insurance status, discharge disposition, comorbidities, and readmission rates were identified as important elements affecting TOC for stroke and TIA. Information from patient surveys indicated that emotional health, follow-up with care providers, stroke education, and point of contact are important elements during the transition periods after stroke and TIA. IMPLICATIONS FOR PRACTICE: Both providers and patients should inform the development of a comprehensive TOC program that spans in-hospital to multiple care settings, including the home, which is essential. The advanced practice nurse is ideally suited to successfully lead these programs.

Associations between working memory, health literacy, and recall of the signs of stroke among older adults.

Stroke remains a major cause of mortality and disability among older adults. Although early treatment after stroke is known to reduce both mortality and disability, the first step in seeking early treatment is dependent on the rapid recognition of the signs of stroke. Recall of the signs of stroke may be dependent on factors that exist before the stroke itself. Although it is known that both working memory and health literacy decline with advancing age, these factors have not been thoroughly examined with respect to recall of the signs of stroke. Therefore, the purpose of the current study was to investigate associations between working memory, health literacy, and recall of the signs of stroke among older adults. Community dwelling older adults (≥65 years of age) were recruited from two senior centers. Fifty-six participants meeting inclusion criteria provided demographic and health information and were asked to read a public service brochure listing the five warning signs of stroke. Working memory was then assessed using the Wechsler Adult Intelligence Scale 3rd Edition Working Memory Index. Health literacy was assessed by the Short Test of Functional Health Literacy in Adults. Participants' recall of the five warning signs of stroke was evaluated. The mean age was 80.4 years. The mean number of the signs of stroke recalled was 2.9 ± 1.33. Working memory and health literacy were positively correlated with recall of the signs of stroke (r = .38, p < 0.01; r = .44, p < 0.01). In a simultaneous regression, only health literacy remained a significant predictor of recall. There was no statistically significant interaction between working memory and health literacy. Findings from this study indicate that working memory and health literacy were associated with successful recall of the warning signs of stroke in older adults. Further studies are needed to determine if programs that include cognitive and literacy assessments could identify older adults who need additional support to learn and recall the signs of stroke.

Whole blood aggregation, coagulation, and markers of platelet activation in diet-induced diabetic C57BL/6J mice.

AIMS: Type 2 diabetes in humans is associated with hypercoaguability; however, little is known about platelet function in mouse models of type 2 diabetes used to study this disorder. Therefore, the purpose of this study was to examine platelet aggregation, coagulation, and markers of platelet activation in a diet-induced mouse model of type 2 diabetes. METHODS: Four week old, male, C57BL/6J mice were randomized to a standard chow or high fat (60% beef lard) diet for 4 months. To examine platelet function we measured ADP-induced whole blood aggregometry, whole blood coagulation by thromboelastography, tail bleeding times, platelet microparticle and platelet expression of p-selectin and platelet expression of CD61 by flow cytometry. RESULTS: Diabetic mice exhibited less aggregation (p<0.05), less coagulation (p<0.01), prolonged tail bleeding times (n.s.), and lower agonist stimulated platelet CD61 expression (p<0.001) compared to non-diabetic mice. There was no difference in platelet microparticle and platelet p-selectin expression. CONCLUSIONS: Diet-induced type 2 diabetic mouse do not demonstrate the hypercoagulability and platelet activation typically observed in humans with this disorder. More studies are warranted to further explore platelet function in this mouse model; to determine their applicability for studying these alterations in type 2 diabetes.

Whole blood aggregation and coagulation in db/db and ob/ob mouse models of type 2 diabetes.

Type 2 diabetes in humans is associated with a significant hypercoagulable state; however, the effects of this on stroke and cardiovascular disease are not completely understood. The genetic mutations in db/db and ob/ob mice produce metabolic abnormalities similar to type 2 diabetes, but little is known about their platelet or coagulation properties. The objective of this study was therefore to examine platelet function and coagulation in db/db and ob/ob mice to determine the degree of alteration induced by type 2 diabetes. Male db/db and ob/ob mice, 8-16 weeks old, and their respective genetic control mice were used for all experiments. To examine platelet function and coagulation, we measured ADP-induced whole blood aggregation at baseline and after inhibition with aspirin and fucoidan, whole blood coagulation by thromboelastography, and platelet CD61 expression by flow cytometry. Both db/db and ob/ob mice demonstrated significantly less ADP-induced whole blood aggregation compared with control mice (db/db mice, P < 0.001; ob/ob mice, P < 0.01). Aggregation was significantly inhibited with aspirin in all groups; however, fucoidan inhibited aggregation only in control mice. The db/db and ob/ob mice demonstrated significantly less maximal clot strength compared with control mice (P < 0.01), and ob/ob mice demonstrated premature clot fibrinolysis measured by thromboelastography. In conclusion, the db/db and ob/ob type 2 diabetes mouse models do not demonstrate a hypercoagulable state similar to humans with this disease. We caution their use for studying cardiovascular and cerebrovascular disease in the setting of type 2 diabetes.

Comparison of sample fixation and the use of LDS-751 or anti-CD45 for leukocyte identification in mouse whole blood for flow cytometry.

Flow cytometry methods used to measure leukocyte function often entail sample preparation procedures that cause artifactual cell activation. To avoid leukocyte activation by isolation techniques, some preparation methods use fluorescent markers to discriminate leukocytes from erythrocytes in whole blood. One of these markers, laser dye styryl-751(LDS-751), has been used to distinguish leukocytes by staining nucleic acid, but has been found to stain other blood cells and dead cells indiscriminately. Thus, LDS-751 may not be an appropriate reagent for leukocyte identification in whole blood. Fixing samples with formaldehydes increases cell permeability and causes surface protein cross-linking that may alter staining of both intra- and extracellular markers. The degree of this sample alteration by formaldehyde fixation, however, remains in question. In addition, little is known about flow cytometry and sample preparation methods in mouse whole blood. The purpose of this study was to determine if labeling leukocytes with a monoclonal antibody specific to leukocyte common antigen (CD45) was superior to labeling with LDS-751 and to determine the effect of sample fixation on a mouse whole blood preparation for flow cytometry. Samples were incubated with CD16/CD32 Fc receptor blocker, and either 10 microg/ml LDS-751 or phosphate buffered saline (PBS). The samples were then fixed with paraformaldehyde or diluted with PBS followed by incubation with 5 microg/ml PerCP-conjugated anti-CD45, 5 microg/ml FITC-conjugated anti-CD11b, or 80 microM dichlorofluorescein diacetate. We found that samples labeled with LDS-751 demonstrated decreased fluorescence intensity for granulocyte CD11b expression and ROS production compared to samples labeled with anti-CD45. In addition, sample fixation decreased mean fluorescence intensity in samples labeled with either LDS-751 or anti-CD45. We conclude that labeling leukocytes with monoclonal antibody CD45 in a mouse whole blood preparation is preferable, as it provides improved measurement of leukocyte indices compared to LDS-751. Also, while sample fixation prior to antibody staining caused a decrease in overall fluorescence; it can be used to successfully identify extra-cellular markers.

Leukocyte-platelet aggregates in rat peripheral blood after ischemic stroke and reperfusion.

Ischemic stroke and reperfusion (ISR) is associated with an inflammatory response characterized, in part, by the formation of leukocyte-platelet aggregates (LPA). Aggregate formation may amplify the immunologic and hemostatic functions of both cell types and thus exacerbate reperfusion injury after ischemic stroke. LPA formation in peripheral blood may also serve as a biomarker of the severity of injury. However, it is not fully known whether ISR causes LPA formation that can be detected in the peripheral blood. Therefore, the purpose of this study was to measure LPA in the peripheral blood after ISR using a rat model. The filament method was used to perform ISR. Blood was collected from the jugular vein before ischemia, after 4 hours of ischemia, and after 1 hour of reperfusion. Flow cytometry was used to quantify LPA in peripheral blood. Separate ISR groups were treated with tirofiban, a platelet GPIIb/IIIa inhibitor, and fucoidan, a selectin adhesion molecule inhibitor, and analyzed for LPA. Leukocyte CD11b expression and reactive oxygen species production were also analyzed to note the role of polymorphonuclear neutrophilic (PMN) activation on LPA formation. After ISR, LPA levels in peripheral blood were twice as large as preischemic levels. Both GPIIb/IIIa and selectin adhesion molecule inhibition (p < .05) decreased LPA to preischemic values. PMN CD11b expression was increased above baseline but did not differ between groups. Reactive oxygen species production did not differ between groups during reperfusion. These data suggest that ischemic stroke and reperfusion results in an increase in LPA that can be consistently measured in peripheral blood. LPA formation may be a useful biomarker and potential therapeutic target after ischemic stroke and reperfusion.

Parathyroid hormone-related protein induction in focal stroke: a neuroprotective vascular peptide.

Parathyroid hormone-related protein (PTHrP) is a multifunctional peptide that enhances blood flow in non-central nervous system (CNS) vascular beds by causing vasodilation. PTHrP expression is induced in non-CNS organs in response to ischemia. Experiments were therefore undertaken to determine whether PTHrP can be induced in brain in response to ischemic injury and whether PTHrP can act locally as a vasodilator in the cerebral vasculature, an effect that could be neuroprotective in the setting of stroke. PTHrP expression was examined by Northern analysis and immunohistochemical staining in male Sprague-Dawley rats subjected to permanent middle cerebral artery occlusion (MCAO). Vasodilatory effects of superfused PTHrP(1-34) on pial arterioles were determined by intravital fluorescence microscopy. Effects of PTHrP(1-34) peptide administration on MCAO infarction size reduction were assessed. PTHrP expression was induced in the ischemic hemisphere as early as 4 h after MCAO and remained elevated for up to 24 h. Increased immunoreactive PTHrP at sites of ischemic tissue injury was located in the cerebral microvessels. Superfusion with PTHrP(1-34) peptide for up to 25 min increased pial arteriolar diameter by 30% in normal animals. In animals with permanent MCAO, PTHrP(1-34) peptide treatment significantly decreased cortical infarct size (-47%). In summary, PTHrP expression increases at sites of ischemic brain injury in the cerebrovasculature. This local increase in PTHrP could be an adaptive response that enhances blood flow to the ischemic brain, thus limiting cell injury.

Protective effects of inhibiting both blood and vascular selectins after stroke and reperfusion.

Early intervention after acute ischemic stroke is essential to minimize brain cell injury. Although reperfusion of the ischemic brain is the treatment of choice for acute stroke, reperfusion itself may cause additional injury. The inflammatory cascade, characterized in part by early leukocyte interaction with endothelium, may contribute to this additional injury to blood vessels and surrounding brain tissue, extending the area of infarction. The selectin family of adhesion molecules mediates the initial, rolling and tethering of leukocytes to endothelium. P-selectin is rapidly expressed on ischemic endothelium in the brain vasculature, and L-selectin is expressed on leukocytes. Blocking the selectin-mediated tethering step may limit the inflammatory component of reperfusion injury in the brain. Fucoidin (FCN), a competitive inhibitor of P- and L-selectin, has been reported to decrease leukocyte accumulation during reperfusion of other organs. The effect of both leukocyte and endothelial selectin inhibition after cerebral ischemia and reperfusion has not been previously examined. The purpose of this study was to determine the effects of selectin adhesion molecule blockade on cerebral infarction size and neurological function after middle cerebral artery occlusion and reperfusion (MCAO-R) in the rat. MCAO was induced using the filament method. All animals were subjected to 4 h of MCAO and 24 h of reperfusion. After 24 h, brains were analyzed for size of infarction. Neurological function was assessed during stroke and 24 h after reperfusion. Two groups were studied, an untreated control group (n = 9) and a group treated with the selectin inhibitor, fucoidin (25 mg kg(-1)) (n = 9). We found that selectin blockade significantly reduced cerebral infarction size by 50% (p < 0.05) and improved neurological function (p < 0.05). In addition, a trend toward decreased cerebral edema was demonstrated with selectin inhibition. These results indicate that treatment of the blood and the endothelium with a selectin anti-inflammatory agent is protective after focal stroke and reperfusion in the rat.