Dataset Information

The Long-Term Outcome Comparison of Different Time-Delayed Kallikrein Treatments in a Mouse Cerebral Ischemic Model.

ABSTRACT: Delayed administration of kallikrein after cerebral infarction can improve neurological function. However, the appropriate kallkrein treatment time after ischemic stroke has not been illuminated. In this study, we compared the long-term outcome among three kallikrein therapeutic regimens starting at different time points following mouse cerebral ischemia. Furthermore, the protective mechanisms involving neurogenesis, angiogenesis, and AKT-GSK3?-VEGF signaling pathway were analyzed. Human tissue kallikrein was injected through the tail vein daily starting at 8?h, 24?h, or 36?h after right middle cerebral artery occlusion (MCAO) until the 28th day. Three therapeutic regimens all protected against neurological dysfunction, but kallikrein treatment starting at 8?h after MCAO had the best efficacy. Additionally, kallikrein treatment at 8?h after MCAO significantly enhanced cell proliferation including neural stem cell and induced differentiation of neural stem cell into mature neuron. Kallikrein treatment starting at 8?h also promoted more angiogenesis than other two treatment regimens, which was associated with AKT-GSK3?-VEGF signaling pathway. Thus, we confirm that three delayed kallikrein treatments provide protection against cerebral infarction and furthermore suggest that kallikrein treatment starting at 8?h had a better effect than that at 24?h and 36?h. These findings provide the experimental data contributing to better clinical application of exogenous kallikrein.

SUBMITTER: Ni Y

PROVIDER: S-EPMC5907522 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Long-Term Outcome Comparison of Different Time-Delayed Kallikrein Treatments in a Mouse Cerebral Ischemic Model.

Ni Yaohui Y Cai Kefu K Hu Yujie Y Wang Chuan-Hui CH Zhang Yuanyuan Y Huang Hua H Su Xing X Gu Jin-Hua JH

Stem cells international 20180405

Delayed administration of kallikrein after cerebral infarction can improve neurological function. However, the appropriate kallkrein treatment time after ischemic stroke has not been illuminated. In this study, we compared the long-term outcome among three kallikrein therapeutic regimens starting at different time points following mouse cerebral ischemia. Furthermore, the protective mechanisms involving neurogenesis, angiogenesis, and AKT-GSK3<i>β</i>-VEGF signaling pathway were analyzed. Human ...[more]

PMID: 29760720

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Project description:PurposeThis study aims to investigate the agreement of three software packages in measuring baseline ischemic core volume (ICV) and penumbra volume (PV), and determine their predictive values for unfavorable clinical outcome in patients with endovascular thrombectomy (EVT).MethodsPatients with acute ischemic stroke who underwent computed tomographic perfusion (CTP) were recruited. Baseline CTP measurements including ICV and PV were calculated by three software packages of IntelliSpace Portal (ISP), Rapid Processing of Perfusion and Diffusion (RAPID), and fast-processing of ischemic stroke (F-STROKE). All patients received EVT, and the modified Rankin scale (mRS) at 90 days after EVT was assessed to determine the clinical outcomes (favorable: mRS = 0-2; unfavorable: mRS = 3-6). The agreement of CTP measurements among three software packages was determined using intraclass correlation coefficient (ICC). The associations between CTP measurements and unfavorable clinical outcome were analyzed using logistic regression. Receiver operating characteristic curves were conducted to calculate the area under the curve (AUC) of CTP measurements in predicting unfavorable clinical outcome.ResultsOf 223 recruited patients (68.2 ± 11.3 years old; 145 males), 17.0% had unfavorable clinical outcome after EVT. Excellent agreement between F-STROKE and RAPID was found in measuring ICV (ICC 0.965; 95% CI 0.956-0.973) and PV (ICC 0.966; 95% CI 0.956-0.973). ICVs measured by three software packages were significantly associated with unfavorable clinical outcome before (odds ratios 1.012-1.018, all P < 0.01) and after (odds ratios 1.003-1.014, all P < 0.05) adjusted for confounding factors (age, gender, TOAST classification, and NIHSS on admission). In predicting unfavorable clinical outcome, ICV measured by F-STROKE showed similar performance to that measured by RAPID (AUC 0.701 vs. 0.717) but higher performance than that measured by ISP (AUC 0.629).ConclusionsThe software of F-STROKE has excellent agreement with the widely used analysis tool of RAPID in measuring ICV and PV. The ischemic core volume measured by both F-STROKE and RAPID is a stronger predictor for unfavorable clinical outcome after EVT compared to ISP.

Project description:Background and purposeDCI is a serious complication following aneurysmal SAH and remains a leading cause of morbidity and mortality. Our aim was to evaluate CTP in aneurysmal SAH by using outcome measures of DCI.Materials and methodsThis was a retrospective study of consecutive patients with SAH enrolled in a prospective institutional review board-approved clinical accuracy trial. Qualitative CTP deficits were determined by 2 neuroradiologists blinded to clinical and imaging data. Quantitative CTP was performed by using a standardized protocol with region-of-interest placement sampling of the cortex. Primary outcome measures were permanent neurologic deficits and infarction. The secondary outcome measure was DCI, defined as clinical deterioration. CTP test characteristics (95% CI) were determined for each outcome measure. Statistical significance was calculated by using the Fisher exact and Student t tests. ROC curves were generated to determine accuracy and threshold analysis.ResultsNinety-six patients were included. Permanent neurologic deficits developed in 33% (32/96). CTP deficits were seen in 78% (25/32) of those who developed permanent neurologic deficits and 34% (22/64) of those without (P < .0001). CTP deficits had 78% (61%-89%) sensitivity, 66% (53%-76%) specificity, and 53% (39%-67%) positive and 86% (73%-93%) negative predictive values. Infarction occurred in 18% (17/96). CTP deficits were seen in 88% (15/17) of those who developed infarction and 41% (32/79) of those without (P = .0004). CTP deficits had an 88% (66%-97%) sensitivity, 59% (48%-70%) specificity, and 32% (20%-46%) positive and 96% (86%-99%) negative predictive values. DCI was diagnosed in 50% (48/96). CTP deficits were seen in 81% (39/48) of patients with DCI and in 17% (8/48) of those without (P < .0001). CTP deficits had 81% (68%-90%) sensitivity, 83% (70%-91%) specificity, and 83% (70%-91%) positive and 82% (69%-90%) negative predictive values. Quantitative CTP revealed significantly reduced CBF and prolonged MTT for DCI, permanent neurologic deficits, and infarction. ROC analysis showed that CBF and MTT had the highest accuracy.ConclusionsCTP may add prognostic information regarding DCI and poor outcomes in aneurysmal SAH.

Dataset Information

The Long-Term Outcome Comparison of Different Time-Delayed Kallikrein Treatments in a Mouse Cerebral Ischemic Model.

Publications

The Long-Term Outcome Comparison of Different Time-Delayed Kallikrein Treatments in a Mouse Cerebral Ischemic Model.

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