Cerebral Hypoxia and Ischemia in the Pathogenesis of Dementia after Stroke

While it has been reported that ischemic stroke significantly increases the risk of delayed dementia,1,2 the underlying mechanisms are not well understood. Hypoxic and ischemic (HI) injury resulting from cerebral hypoperfusion due to systemic illness has been proposed as a pathogenic mechanism in certain subgroups of patients.1,3 Thus, the aim of this study was to investigate whether cerebral HI injury resulting from certain systemic illnesses (e.g., cardiac arrhythmias, cardiac failure, pneumonia, seizures, sepsis) would be an independent risk factor for the development of incident dementia after ischemic stroke

Dementia after Stroke Increases the Risk of Long-Term Stroke Recurrence

Background: Although risk factors for first stroke have been identified, the predictors of long-term stroke recurrence are less well understood. We performed the present study to determine whether dementia diagnosed three months after stroke onset is an independent risk factor for long-term stroke recurrence. Methods: We examined 242 patients (age = 72.0 ± 8.7 years) hospitalized with acute ischemic stroke who had survived the first three months without recurrence and followed them to identify predictors of long-term stroke recurrence. We diagnosed dementia three months after stroke using modified DSM-III-R criteria based on neuropsychological and functional assessments. The effects of conventional stroke risk factors and dementia status on survival free of recurrence were estimated using Kaplan-Meier analyses, and the relative risks (RR) of recurrence were calculated using Cox proportional hazards models. Results: Dementia (RR = 2.71, 95% CI = 1.36 to 5.42); cardiac disease (RR = 2.18, CI = 1.15 to 4.12); and sex, with women at higher risk (RR = 2.03, CI = 1.01 to 4.10), were significant independent predictors of recurrence, while education (RR = 1.90, CI = 0.77 to 4.68), admission systolic blood pressure >160 mm Hg (RR = 1.80, CI = 0.94 to 3.44) and alcohol intake exceeding 160 grams per week (RR = 1.86, CI = 0.79 to 4.38) were weakly related. Conclusions: Our results suggest that dementia significantly increases the risk of long-term stroke recurrence, with additional independent contributions by cardiac disease and sex. Cognitive impairment may be a surrogate marker for multiple vascular risk factors and larger infarct volume that may serve to increase the risk of recurrence. Alternatively, less aggressive medical management of stroke patients with cognitive impairment or noncompliance of such patients with medical therapy may be bases for an increased rate of stroke recurrence

Early Clinical Differentiation of Cerebral Infarction from Severe Atherosclerotic Stenosis and Cardioembolism

Background and Purpose: Hyperacute Cerebral Infarction Trials Require Early Differentiation of Infarction Subtype. Our Aim Was to Determine Clinical Factors Predictive of Infarction Subtype from Data Collected in the Early Hours of Admission. Methods: using the 1,273 Patients Enrolled in the Stroke Data Bank, Stroke Risk Factors and Demographic, Clinical, and Radiological Features Were Compared between the 246 Cardioembolic and 113 Large-Vessel Atherosclerotic Cerebral Infarcts. Results: Stroke Data Bank Definitions Ensured More Transient Ischemic Attacks in Atherosclerotic Infarcts and More Cardiac Disease in Cardioembolic Infarcts, But the Diagnosis Was Distinguished Further using a Logistic Regression Model. Fractional Arm Weakness (Shoulder Different from Hand) (Odds Ratio 3.1, 95% Confidence Interval [CI] 1.6-5.8), Hypertension (Odds Ratio 2.8, CI 1.4-5.3), Diabetes (Odds Ratio 2.5, CI 1.2-5.1) and Male Gender (Odds Ratio=2.2, CI 1.2-4.1) Occurred More Frequently in Patients with Atherosclerotic Than Cardioembolic Infarcts. Reduced Consciousness (Odds Ratio=3.2, CI 1.4-7.3) Was More Frequent in Cardio embolism. for a Male Patient with Hypertension, Diabetes, and Fractional Arm Weakness, the Estimated Odds of an Atherosclerotic Infarction Were 47-Fold that of a Cardioembolic Infarction. Patients with Atherosclerotic Infarcts Were More Likely to Have a Fractional Arm Weakness Regardless of Infarct Size, Whereas, for Those with Cardioembolic Infarctions, Fractional Weakness Was More Frequent in Infarcts Less Than 20 Cc in Volume. Conclusions: Clinical Features that Are Observed at Stroke Onset Can Help Distinguish Cerebral Infarction Subtypes and May Allow for Early Stratification in Therapeutic Trials. © 1992 American Heart Association, Inc

Altered expression of a putative progenitor cell marker DCAMKL1 in the rat gastric mucosa in regeneration, metaplasia and dysplasia

<p>Abstract</p> <p>Background</p> <p>Doublecortin and calcium/calmodulin-dependent protein kinase-like-1 (DCAMKL1) is a candidate marker for progenitor cells in the gastrointestinal mucosa. Lineage cells in the gastric mucosa are derived from progenitor cells, but this process can be altered after injury. Therefore, we explored DCAMKL1 expression under pathological conditions.</p> <p>Methods</p> <p>An immunohistochemical analysis was performed in rat stomach with acute superficial injury, chronic ulcer, intestinal metaplasia and dysplasia.</p> <p>Results</p> <p>DCAMKL1 was exclusively expressed in immature quiescent cells in the isthmus of normal fundic glands, where putative progenitor cells are thought to reside. DCAMKL1-positive cells and proliferating cells shed into the lumen after superficial injury and re-appeared during the regenerative process, mainly in the superficial mucosa. In the marginal mucosa around the active ulcer, parietal and chief cells diminished, foveolar hyperplasia was evident, and trefoil factor family 2 (TFF2)/spasmolytic polypeptide-expressing metaplasia (SPEM) emerged at the gland base. DCAMKL1 cells re-emerged in the deep mucosa juxtaposed with SPEM and proliferating cells. In the healing ulcer, the TFF2 cell population expanded and seemed to redifferentiate to chief cells, while proliferating cells and DCAMKL1 cells appeared above and below the TFF2 cells to promote healing. SPEM appeared and PCNA cells increased in the intestinalized mucosa, and DCAMKL1 was expressed in the proximity of the PCNA cells in the deep mucosa. DCAMKL1, PCNA and TFF2 were expressed in different dysplastic cells lining dilated glands near SPEM.</p> <p>Conclusion</p> <p>The ultrastructural appearance of DCAMKL1-positive cells and the expression patterns of DCAMKL1 in normal and pathological states indicate that the cells belong to a progenitor cell population. DCAMKL1 expression is closely associated with TFF2/SPEM cells after injury. DCAMKL1 cells repopulate close to proliferating, hyperplastic, metaplastic and dysplastic cells, and the progenitor zone shifts according to the pathological circumstances.</p