Among the various perspectives on cerebrovascular diseases, hemodynamic analysis-which has recently garnered interest-is of great help in understanding cerebrovascular diseases. Computational fluid ...dynamics (CFD) analysis has been the primary hemodynamic analysis method, and studies on cerebral aneurysms have been actively conducted. However, owing to the intrinsic limitations of the analysis method, the role of wall shear stress (WSS), the most representative parameter, remains controversial. High WSS affects the formation of cerebral aneurysms; however, no consensus has been reached on the role of WSS in the growth and rupture of cerebral aneurysms. Therefore, this review aimed to briefly introduce the up-to-date results and limitations made through CFD analysis and to inform the need for a new hemodynamic analysis method.
In the hemodynamic study, computational fluid dynamics (CFD) analysis has shown that high wall shear stress (WSS) is an important parameter in cerebral aneurysm formation. However, CFD analysis is ...not more realistic than fluid-structure interaction (FSI) analysis given its lack of considering the involvement of vascular structures. To investigate the relationship between the hemodynamic parameters and the aneurysm formation, the locations of high WSS and high strain were extracted from the CFD and FSI analyses, respectively. Then the distances between the aneurysm formation site and the locations of high WSS or high strain were calculated. A total of 37 intracranial paraclinoid aneurysms were enrolled for quantitative comparison. Additionally, the dura mater was modeled to facilitate realistic results in FSI analysis. The average distance from the location of the aneurysm formation site to the high strain (1.74 mm Formula: see text 1.04 mm) was smaller than the average distance to the high WSS (3.33 mm Formula: see text 1.18 mm). The presence of dura mater also influenced the findings in the aneurysm formation site. High strain extracted by FSI analysis is an important hemodynamic factor related to the formation of cerebral aneurysms. Strain parameter could help to predict the formation of aneurysms and elucidate the appropriate treatment.
This study aimed to evaluate the safety and efficacy of intra-arterial (IA) administration of low- dose tirofiban during endovascular therapy in patients with large ischemic core volumes on initial ...brain CT. Patients were divided into two groups based on the use of IA tirofiban. We identified 87 patients (16 and 71 patients in the tirofiban and no-tirofiban groups, respectively) with acute ischemic stroke due to intracranial artery occlusion who underwent endovascular therapy with a low Alberta Stroke Program Early CT scores (2-5). Multivariate logistic regression analysis revealed no association between IA tirofiban administration and serious postprocedural hemorrhagic complications (adjusted odds ratio (aOR), 0.720; 95% confidence interval (CI) 0.099-5.219; p = 0.960), any radiologic hemorrhage (aOR 0.076; 95% CI 0.003-2.323; p = 0.139), or 3-month mortality (aOR, 0.087; 95% CI 0.005-1.501; p = 0.093). However, IA tirofiban was associated with a lower 90-day mRS score (aOR, 0.197; 95% CI 0.015-1.306; p = 0.017) and change of NIHSS compared with baseline (aOR, 0.698; 95% CI 0.531-0.917; p = 0.010). IA tirofiban administration during endovascular therapy in patients with large ischemic core volumes may be effective and safe.
Cerebral aneurysms should be treated on the basis of accurate rupture risk prediction. Nowadays, the rupture risk in aneurysms has been estimated using hemodynamic parameters. In this paper, we ...suggest a new way to predict the rupture risks in cerebral aneurysms by using fluid-structure interaction (FSI) analysis for better decision-making regarding treatment. A patient-specific model was constructed using digital subtraction angiography of 51 cerebral aneurysms. For each model, a thin-walled area (TWA) was first predicted using computational fluid dynamics (CFD), and then the highest equivalent strain in the TWA was calculated with FSI by varying wall thicknesses and mechanical properties. A critical curve was made from 16 FSI results for each patient-specific model to estimate the rupture risk. On average, the equivalent strains of the ruptured aneurysms were higher than those of the unruptured aneurysms. Furthermore, the patterns of critical curves between unruptured and ruptured aneurysms were clearly distinguishable. From the rupture risk evaluation based on the cut-off value, 24 of the 27 unruptured aneurysms and 15 of the 24 ruptured aneurysms were matched with actual-clinical setting cases. The critical curve proposed in the present study could be an effective tool for the prediction of the rupture risk of aneurysm.
Numerous studies have evaluated the effects of hemodynamic parameters on aneurysm formation. However, the reasons why aneurysms do not initiate in intracranial arteries are still unclear. This study ...aimed to investigate the influence of hemodynamic parameters, wall shear stress (WSS) and strain, on aneurysm formation by comparing between aneurysmal and non-aneurysmal arteries. Fifty-eight patients with paraclinoid aneurysms on one side were enrolled. Based on magnetic resonance angiography, each patient's left and right internal carotid arteries (ICAs) were reconstructed. For a patient having an aneurysm on one side, the ICA with the paraclinoid aneurysm was defined as the aneurysmal artery after eliminating the aneurysm, whereas the opposite ICA without aneurysm was defined as the non-aneurysmal artery. Computational fluid dynamics and fluid-structure interaction analyses were then performed for both aneurysmal and non-aneurysmal arteries. Finally, the relationship between high hemodynamic parameters and aneurysm location was investigated. For aneurysmal arteries, high WSS and strain locations were well-matched with the aneurysm formation site. Also, considerable correlations between high WSS and strain locations were observed. However, there was no significant relationship between high hemodynamic parameters and aneurysm formation for non-aneurysmal arteries. The findings are helpful for understanding aneurysm formation mechanism and encouraging further relevant research.
Object. Rupture of a cerebral aneurysm occurs mainly in a thin-walled area (TWA). Prediction of TWAs would help to assess the risk of rupture and select appropriate treatment strategy. There are ...several limitations of current prediction techniques for TWAs. To predict TWAs more accurately, HP should be normalized to minimize the influence of analysis conditions, and the effectiveness of normalized, combined hemodynamic parameters (CHPs) should be investigated with help of the quantitative color analysis of intraoperative images. Methods. A total of 21 unruptured cerebral aneurysms in 19 patients were analyzed. A normalized CHP was newly suggested as a weighted average of normalized wall shear stress (WSS) and normalized oscillatory shear index (OSI). Delta E from International Commission on Illumination was used to more objectively quantify color differences in intraoperative images. Results. CFD analysis results indicated that WSS and OSI were more predictive of TWAs than pressure (P<.001, P=.187, P=.970, respectively); these two parameters were selected to define the normalized CHP. The normalized CHP became more statistically significant (P<.001) as the weighting factor of normalized WSS increased and that of normalized OSI decreased. Locations with high CHP values corresponded well to those with high Delta E values (P<.001). Predicted TWAs based on the normalized CHP showed a relatively good agreement with intraoperative images (17 in 21 cases, 81.0%). Conclusion. 100% weighting on the normalized WSS produced the most statistically significant result. The normalization scheme for WSS and OSI suggested in this work was validated using quantitative color analyses, rather than subjective judgments, of intraoperative images, and it might be clinically useful for predicting TWAs of unruptured cerebral aneurysms. The normalization scheme would also be integrated into further fluid-structure interaction analysis for more reliable estimation of the risk of aneurysm rupture.
Protein kinase C‐δ (PKCδ) is a diacylglycerol‐dependent, calcium‐independent novel PKC isoform that is engaged in various cell signaling pathways, such as cell proliferation, apoptosis, inflammation, ...and oxidative stress. In this study, we searched for proteins that bind PKCδ using a yeast two‐hybrid assay and identified murine arrest‐defective 1 (mARD1) as a binding partner. The interaction between PKCδ and mARD1 was confirmed by glutathione S‐transferase pull‐down and co‐immunoprecipitation assays. Furthermore, recombinant PKCδ phosphorylated full‐length mARD1 protein. The NetPhos online prediction tool suggested PKCδ phosphorylates Ser80, Ser108, and Ser114 residues of mARD1 with the highest probability. Based on these results, we synthesized peptides containing these sites and examined their phosphorylations using recombinant PKCδ. Autoradiography confirmed these sites were efficiently phosphorylated. Consequent mass spectrometry and peptide sequencing in combination with MALDI‐TOF MS/MS confirmed that Ser80 and Ser108 were major phosphorylation sites. The alanine mutations of Ser80 and Ser108 abolished the phosphorylation of mARD1 by PKCδ in 293T cells supporting these observations. In addition, kinase assays using various PKC isotypes showed that Ser80 of ARD1 was phosphorylated by PKCβI and PKCζ isotypes with the highest selectivity, while Ser108 and/or Ser114 were phosphorylated by PKCγ with activities comparable to that of the PKCδ isoform. Overall, these results suggest the possibility that PKCδ transduces signals by regulating phosphorylation of ARD1.
A yeast two‐hybrid assay identified murine arrest‐defective 1 (mARD1) as a binding partner of protein kinase c‐delta. Ser80 and Ser108 were found as phosphorylation sites. Our study suggests the possibility that PKCδ transduces signals by regulating the phosphorylation of ARD1.
Traumatic brain injury (TBI) has been known to accelerate bone healing. Many cells and molecules have been investigated but the exact mechanism is still unknown. The neuroinflammatory state of TBI ...has been reported recently. We aimed to investigate the effect of TBI on fracture healing in patients with tibia fractures and assess whether the factors associated with hematoma formation changed more significantly in the laboratory tests in the fractures accompanied with TBI.
We retrospectively investigated patients who were surgically treated for tibia fractures and who showed secondary bone healing. Patients with and without TBI were divided for comparative analyses. Radiological parameters were time to callus formation and the largest callus ratio during follow-up. Preoperative levels of complete blood count and chemical battery on admission were measured in all patients. Subgroup division regarding age, gender, open fracture, concomitant fracture and severity of TBI were compared.
We included 48 patients with a mean age of 44.9 (range, 17-78), of whom 35 patients (72.9%) were male. There were 12 patients with TBI (Group 1) and 36 patients without TBI (Group 2). Group 1 showed shorter time to callus formation (P < 0.001), thicker callus ratio (P = 0.015), leukocytosis and lymphocytosis (P ≤ 0.028), and lower red blood cell counts (RBCs), hemoglobin, and hematocrit (P < 0.001). Aging and severity of TBI were correlated with time to callus formation and callus ratio (P ≤ 0.003) while gender, open fracture, and concomitant fracture were unremarkable.
Tibia fractures with TBI showed accelerated bone healing and superior measurements associated with hematoma formation (lymphocytes, RBCs, hemoglobin, hematocrit). Promoted fracture healing in TBI was correlated with the enhanced proinflammatory state.
III, case control study.
The autonomic nervous system (ANS) plays an important role in the initiation and maintenance of atrial fibrillation (AF). However, the meaning of higher heart rate variability (HRV) in predicting AF ...remains unclear. Among 2100 patients in the Holter registry, a total of 782 hypertensive patients were included in this study. Baseline HRV was measured by time domain and frequency domain methods using 24-h Holter monitoring. The primary outcome was the development of AF. During an average follow-up of 1.1 years, 44 patients developed AF. Higher HRV parameters including high-frequency (P < 0.001), the square root of the mean squared differences of successive NN intervals (P < 0.001), and the percentage of NN intervals that are more than 50 ms different from the previous interval (P < 0.001) were associated with the occurrence of AF in univariate analysis. Premature atrial contractions burden, lower baseline heart rate, age, hemodialysis, coronary artery disease, and chronic heart failure were also associated with AF. In Cox regression analysis, higher HRV (representing excessive autonomic fluctuation) was an independent risk factor for AF. Excessive autonomic fluctuation represented by higher HRV in patients with hypertension was associated with an increased risk of AF.
Computational fluid dynamics (CFD) has been utilized to calculate hemodynamic parameters in anterior communicating artery aneurysm (AComA), which is located at a junction between left and right A1 ...and A2 segments. However, complete or half circle of Willis (CoW) models are used indiscriminately. This study aims to suggest recommendations for determining suitable CoW model. Five patient-specific CoW models with AComA were used, and each model was divided into complete, left-half, and right-half models. After validating the CFD using a flow experiment, the hemodynamic parameters and flow patterns in five AComAs were compared. In four out of five cases, inflow from one A1 side had a dominant influence on the AComA, while both left and right A1 sides affected the AComA in the remaining case. Also, the average difference in time-averaged wall shear stress between the complete and half models for four cases was 4.6%, but it was 62% in the other case. The differences in the vascular resistances of left and right A1 and A2 segments greatly influenced the flow patterns in the AComA. These results may help to enhance clinicians' understanding of blood flow in the brain, leading to improvements in diagnosis and treatment of cerebral aneurysms.
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