Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Levetiracetam inhibits THP-1 monocyte chemotaxis and adhesion via the synaptic vesicle 2A.

Long-term therapy with older antiepileptic drugs (AEDs), but not levetiracetam (LEV), may increase the risk of atherosclerosis (AS), suggesting that LEV may have a potential anti-AS effect. The synaptic vesicle 2A (SV2A) is known to the specific binding site of LEV. Numerous studies have documented that SV2A is a membrane protein specifically expressed in nervous system. Interestingly, our previous research showed that SV2A also existed in human CD8+ T lymphocytes. Therefore, we hypothesized that LEV was associated with decreased risk of AS by regulating monocytes chemotaxis and adhesion. We showed that SV2A protein were detected in THP-1 human monocytic leukemia cells. LEV (300 µM) inhibited the chemotaxis and adhesion of THP-1 cells after transfection with plasmids expressing SV2AWT, but not SV2AR383Q which was a known functional mutation site of human SV2A. Furthermore, RT-PCR and western blot analysis demonstrated that LEV (300 µM) decreased the expression level of chemokine-related receptors (CX3CL1, CCR1, CCR2, and CCR5),and reduced levels of phosphorylated AKT (p-AKT) in THP-1 cells with SV2AWT expressing plasmids. Taken together, these findings indicated that LEV has an inhibitory effect on THP-1 monocyte adhesion and chemotaxis, suggesting that SV2A may serve as a novel therapeutic target to prevent AS.

Effect of rt-PA intravenous thrombolysis on the prognosis of patients with minor ischemic stroke.

AIMS: The evidence of rt-PA intravenous thrombolysis in patients with minor ischemic stroke (MIS) is still controversial. This study aims to investigate the effect of rt-PA intravenous thrombolysis on the prognosis of patients with MIS. METHODS: We continuously enrolled and analyzed patients with MIS admitted into our hospital within 24 h after symptom onset between January 2016 and December 2018, including 96 patients received intravenous thrombolysis within 4.5 h after symptom onset and 84 patients not received intravenous thrombolysis. A favorable long-term outcome was a 90-day mRS score of 0-1. Good short-term outcome was a 7-day NIHSS score of 0 or less than NIHSS onset. RESULTS: There were no statistical differences between two groups of patients' age, gender, history of hypertension, coronary heart disease, atrial fibrillation, smoking, drinking, and baseline NIHSS score. Patients with history of stroke (22.62% vs. 10.42%, p < 0.05) and diabetes (46.43% vs. 22.92%, p = 0.01) were higher in group of non-thrombolysis. The difference of NIHSS score after 7 days was statistically different between the two groups (p < 0.05), while there was no significant difference in 90-day mRS score. Logistic regression analysis indicated that the prognosis of patients was correlated with neutrophil ratio and CRP at admission. CONCLUSION: Patients with MIS received intravenous thrombolysis may be associated with earlier neurological improvement, but might has no significant effect on long-term prognosis. The level of neutrophil ratio and CRP at admission are risk factors determining the prognosis, which requires further research.

Increased GABAergic development in iPSC-derived neurons from patients with sporadic Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and the underlying molecular mechanisms of this neurodegenerative disorder are still unclear. γ-Aminobutyric acid (GABA) neurons play an essential role in the excitatory/inhibitory (E/I) balance in the brain, and the GABAergic system may contribute to the pathogenesis of AD. We used human induced pluripotent stem cells (iPSCs) generated from sporadic AD (SAD) patients to analyze the phenotype and transcriptional profiles of SAD iPSC-derived neural cells. We observed reduced neurogenesis and increased astrogenesis in SAD neural differentiation. We discovered elevated levels of GABA, glutamate decarboxylase 67 (GAD67), and vesicular GABA transporter (vGAT) in SAD neurons that indicated increased GABAergic development. Gene expression profiling of SAD neural cultures showed upregulation of the GABAergic signaling pathway and downregulation of the neurogenesis pathway. We presumed that the GABAergic transmission system might be enhanced in SAD neurons, as an early pathological change of SAD, which provides a novel target and new direction for the development of more effective therapeutic strategies.