Whole-brain CT Perfusion at Admission and During Delayed Time-window Detects the Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To evaluate the utility of computed tomography perfusion (CTP) both at admission and during delayed cerebral ischemia time-window (DCITW) in the detection of delayed cerebral ischemia (DCI) and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage. METHODS: Eighty patients underwent CTP at admission and during DCITW. The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group, and comparisons were also made between admission and DCITW within each group. The qualitative color-coded perfusion maps were recorded. Finally, the relationship between CTP parameters and DCI was assessed by receiver operating characteristic (ROC) analyses. RESULTS: With the exception of cerebral blood volume (P=0.295, admission; P=0.682, DCITW), there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW. In the DCI group, the extreme parameters were significantly different between admission and DCITW. The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps. For the detection of DCI, mean transit time to the center of the impulse response function (Tmax) at admission and mean time to start (TTS) during DCITW had the largest area under curve (AUC), 0.698 and 0.789, respectively. CONCLUSION: Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW. The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.

Early serum miR-1297 is an indicator of poor neurological outcome in patients with aSAH.

Objective: MiRNAs are important regulators of translation and have been described as biomarkers of a number of cardiovascular diseases, including stroke. The purpose of the study was to determine expression levels of serum miR-1297 in patients with aneurysmal subarachnoid hemorrhage (aSAH), and to assess whether miR-1297 was the prognostic indicator of aSAH. Methods: We treated 128 aSAH patients with endovascular coiling. The World Federation of Neurological Surgeons (WFNS) grades, Hunt-Hess grades, and modified Fisher scores were used to assess aSAH severity. Neurologic outcome was assessed using the Modified Rankin Scale (mRS) at 1-year post-aSAH. Serum was taken at various time points (24, 72, and 168 h, and 14 days). Serum samples from aSAH patients and healthy controls were subjected to reverse transcription (RT) quantitative real-time PCR (RT-qPCR). Results: A poor outcome at 1 year was associated with significantly higher levels of miR-1297 value at the four time points, higher WFNS grade, higher Hunt-Hess grade, and higher Fisher score. Serum miR-1297 levels were significantly higher in patients, compared with healthy controls. There were significant correlations of miR-1297 concentrations in serum with severity in aSAH. The AUCs of miR-1297 at the four time points for distinguishing the aSAH patients from healthy controls were 0.80, 0.94, 0.77, and 0.59, respectively. After multivariate logistic regression analysis, only miR-1297 at 24 and 72 h enabled prediction of neurological outcome at 1 year. Conclusion: Serum was an independent predictive factor of poor outcome at 1 year following aSAH. This result supports the use of miR-1297 in aSAH to aid determination of prognosis.

Stromal cell-derived factor 1α facilitates aneurysm remodeling in elastase-induced rabbit saccular aneurysm.

AIMS: Inflammation plays a crucial role in aneurysm wall remodeling, which could lead to the rupture of intracranial aneurysms. Stromal cell-derived factor 1α (SDF-1α), a vital inflammation cytokine, is also related to aneurysm pathogenesis. However, the characteristics of SDF-1α expression and its role in aneurysm remodeling remain largely unknown. In this study, we aimed to investigate the expression dynamics of SDF-1α and its correlation with aneurysm remodeling. METHODS: Saccular aneurysms were induced by porcine pancreatic elastase in New Zealand White rabbits. Aneurysm size was measured by digital subtraction angiography. Endothelial-like cells on the aneurysm wall were assessed on postoperative days 1, 3, 7, 14, 21, and 30. SDF-1α levels in the aneurysmal wall and serum were examined at several follow-up time points. Adherent molecule expression was examined, and migration assays were performed in vitro. After SDF-1α stimulation, the mobilization of endothelial-lineage cells and its role in the reendothelialization of the aneurysm wall were investigated in a saccular aneurysm rabbit model. RESULTS: After the creation of saccular aneurysms in rabbits, the aneurysm sacs were filled with acute thrombosis within 3days, followed by a significant enlargement on day 14 and maturation on day 21. Serum SDF-1α levels increased in a bimodal fashion on day 1 and day 14, whereas SDF-1α expression in the aneurysm wall reached its maximum on day 14. VE-cadherin was up-regulated after SDF-1α stimulation and down-regulated by the SDF-1α ligand blocker AMD3100. Endothelial progenitor cell migration was enhanced by SDF-1α and blocked by AMD3100. The in vivo administration of SDF-α to rabbits with saccular aneurysms promoted endothelial-lineage cell mobilization into the peripheral blood and reendothelialization of the aneurysm wall. CONCLUSIONS: The SDF-1α expression level in the peripheral blood and local aneurysm wall correlated with the aneurysm remodeling process in rabbits with elastase-induced saccular aneurysms. We conclude that SDF-1α may facilitate aneurysm wall remodeling by up-regulating VE-cadherin expression and mobilizing endothelial-lineage cells.

Serum microRNAs are non-invasive biomarkers for the presence and progression of subarachnoid haemorrhage.

miRNAs are important regulators of translation and have been associated with the pathogenesis of a number of cardiovascular diseases including stroke and may be possible prognostic biomarkers. The purpose of the present study was to determine the expression levels of miRNAs in the sera of subarachnoid haemorrhage (SAH) patients and to evaluate their relationships with the severity and clinical outcome of SAH. Serum samples on day 3 after the onset of SAH were subjected to microarray analysis with Exqion miRCURYTM LNA array and quantitative PCR analysis. Serum samples from SAH patients (n=60) and healthy controls (n=10) were subjected to quantitative PCR analysis. The severities and clinical outcomes of the SAH patients were evaluated with the WFNS grade and the Modified Rankin Scale (mRS). Three miRNAs, miR-502-5p, miR-1297 and miR-4320 were significantly up-regulated in the sera of SAH patients when compared with the healthy controls. The serum miR-502-5p and miR-1297 levels were significantly higher in the patients with severe SAH and a poor outcome than in those with mild SAH and a good outcome (P<0.05). The areas under the receiver operating characteristic (ROC) curves (AUCs) of miR-502-5p, miR-1297 and miR-4320 to distinguish the SAH patients from the healthy controls were 0.958 (P<0.001), 0.950 (P<0.001) and 0.843 (P<0.001) respectively. Taken together, these results indicate that miR-502-5p and miR-1297 are potentially valuable indicators of the diagnosis, severity and prognosis of SAH, and miR-4320 was a potentially valuable indicator of the diagnosis of SAH.

Endothelial progenitor cells contribute to neointima formation in rabbit elastase-induced aneurysm after flow diverter treatment.

AIMS: Endothelial progenitor cells (EPCs) are involved in vascular repair and homeostasis after vascular injuries. In this study, we aimed to explore whether bone marrow (BM)-derived EPCs contribute to neointima formation and reendothelialization in rabbit elastase-induced aneurysm after flow diverter treatment. METHODS: Elastase-induced aneurysms were created in New Zealand male rabbits. Three weeks after model creation, flow diverter was implanted to cover the induced aneurysm neck. Autologous EPCs were isolated from bone marrow, expanded ex vivo, double labeled with Hoechst 33,342 and CFSE(carboxyfluorescein diacetate succinimidyl ester), and transplanted transvenously into the rabbits. The rabbits were assigned into three groups. The first group received autologous transfusion of double-labeled EPCs from the first day after stent implantation, and the second group received transfusion from the fifteenth day. The autologous transfusion was given at a 3-day interval and continued for 2 weeks. Fluorescence-labeled cells were tracked under fluorescence microscope at the aneurysm neck and parent artery in the two groups. The third group was established as control group without EPCs transplantation. Scanning electron microscope was used to investigate the reendothelialization rate between the former two groups and the control group. RESULTS: In the first group, double-positive EPCs were found in 3/5 rabbits and mainly located in the subendothelial space and around the stent struts. In the second group, double-positive EPCs were found in 2/5 rabbits and mainly located on the surface of neointima. More endothelial-like cells were observed on the neointima of aneurysm neck and stented parent artery in the groups with EPCs transplantation than control group without EPCs transplantation, but the difference on the number of these cells did not reach statistical significance. CONCLUSIONS: BM-derived EPCs participate in neointima formation and reendothelialization in elastase-induced aneurysm after flow diverter treatment. The EPCs may differentiate into different cell types according to the stages of neointima formation in vivo.