Therapeutic hypothermia (TH) has been regarded as a promising neuroprotective method for acute ischemic stroke (AIS) for decades. During the development of TH, most researchers focused on improving hypothermic benefits by optimizing treatment processes and conditions. Intravenous thrombolysis and endovascular thrombectomy, for instance, have been introduced into AIS treatment. However, the lack of specialized intervention consumables, especially intervention catheter, led to inaccurate and uncontrolled hypothermic temperature, limited the efficacy of TH. In this review, intervention catheters as well as accessory equipment utilized in TH treatment has been summarized. Hopefully, this review may inspire the future development of TH specialized intervention catheter, enhance the outcome of TH, and neuroprotective efficacy in AIS.
BACKGROUND: The neuroprotective effect of magnesium has been widely discussed, and its effectiveness has been confirmed by animal and clinical trials. However, there are still difficulties in clinical translation in diseases such as cerebral ischemia and subarachnoid hemorrhage. Therefore, it is necessary to analyze the literatures about neuroprotection of magnesium to reveal a more comprehensive knowledge framework, research hotspots and trends in the future. METHODS: Original articles and reviews related to neuroprotective effects of magnesium from 1999 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The bibliometrics CiteSpace 6.2.R4 software was used to conduct co-occurrence/co-citation network analysis and plot knowledge visualization maps. RESULTS: A total of 762 articles from 216 institutions in 64 countries were included in this study. The United States had the largest number of publications, followed by China and Canada. The University of California, UDICE-French Research Universities, and the University of Adelaide were the top three institutions in publication volume. Crowther Caroline A was the most published and cited author. Among the top 10 cited articles, there were seven articles on neuroprotection in preterm infants and three on acute stroke. Keyword cluster analysis obtained 11 clusters, showing that current research hotspots focused on magnesium therapy in neurovascular diseases such as cerebral ischemia, spinal cord injury, subarachnoid hemorrhage, and emerging treatment strategies. CONCLUSION: The neuroprotective effects of magnesium in preterm infants have been extensively studied and adequately confirmed. The therapeutic effects of magnesium on cerebral ischemia and subarachnoid hemorrhage have been demonstrated in animal models. However, the results of clinical studies were not satisfactory, and exploring new therapeutic strategies may be the solution. Recently, the combination of magnesium and hypothermia had great potential in neuroprotective therapy and may become a development trend and hotspot in the future.
Neuroprotective Agents , Subarachnoid Hemorrhage , Infant, Newborn , Animals , Infant , Humans , Neuroprotective Agents/therapeutic use , Magnesium/therapeutic use , Infant, Premature , Cerebral Infarction , Bibliometrics
Acute ischemic stroke (AIS) afflicts millions of individuals worldwide. Despite the advancements in thrombolysis and thrombectomy facilitating proximal large artery recanalization, the resultant distal hypoperfusion, referred to "no-reflow" phenomenon, often impedes the neurological function restoration in patients. Over half a century of scientific inquiry has validated the existence of cerebral "no-reflow" in both animal models and human subjects. Furthermore, the correlation between "no-reflow" and adverse clinical outcomes underscores the necessity to address this phenomenon as a pivotal strategy for enhancing AIS prognoses. The underlying mechanisms of "no-reflow" are multifaceted, encompassing the formation of microemboli, microvascular compression and contraction. Moreover, a myriad of complex mechanisms warrant further investigation. Insights gleaned from mechanistic exploration have prompted advancements in "no-reflow" treatment, including microthrombosis therapy, which has demonstrated clinical efficacy in improving patient prognoses. The stagnation in current "no-reflow" diagnostic methods imposes limitations on the timely application of combined therapy on "no-reflow" post-recanalization. This narrative review will traverse the historical journey of the "no-reflow" phenomenon, delve into its underpinnings in AIS, and elucidate potential therapeutic and diagnostic strategies. Our aim is to equip readers with a swift comprehension of the "no-reflow" phenomenon and highlight critical points for future research endeavors.
Ischemic Stroke , No-Reflow Phenomenon , Stroke , Animals , Humans , No-Reflow Phenomenon/diagnostic imaging , No-Reflow Phenomenon/therapy , Thrombectomy , Treatment Outcome , Stroke/diagnostic imaging , Stroke/therapy
Background The relationship between ischemic stroke (IS) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is still unclear, and there is a dearth of stratified research on the relationship between Lp-PLA2 activity and different IS subtypes. Therefore, Mendelian randomization was used in this study to examine the relationship between genetically proxied Lp-PLA2 activity and the risks of IS and its subtypes. Methods Based on information from a meta-analysis of GWAS, which included 13,664 European people, five single-nucleotide polymorphisms related to Lp-PLA2 activity were chosen as instrumental variables. Summary statistics information about MEGESTROKE consortium with the European group (40,585 cases and 406,111 controls) include any ischemic stroke (AIS) (n = 34,217); large-artery stroke (LAS, n=4,373), cardioembolic stroke (CES, n=7,193) and small vessel stroke (SVS, n=5,386). In order to determine the causal relationships between Lp-PLA2 activity and IS as well as its subtypes, the inverse variance weighted (IVW) approach was chosen as the primary analysis. Significant estimates were then tested by sensitivity analysis to rule out heterogeneity and pleiotropy. Results IVW showed Lp-PLA2 activity was causally associated with LAS (OR=3.25, 95% CI=1.65-6.41, p=0.0007), but not with other subtypes of stroke. Sensitivity analysis for causal estimates between Lp-PLA2 activity and LAS showed no significant heterogeneity or pleiotropy. Conclusions These MR analyses support a causal effect of Lp-PLA2 activity on LAS but not on AIS, CES or SVS, which suggests that serum Lp-PLA2 activity might be a biomarker for prediction of LAS.
OBJECTIVE: Hemolysis performance is a crucial criterion for roller pumps utilized in life supporting system. In this study, the factor of hemolysis for roller pumps was selected as the target, and an estimation formulation was built to evaluate its hemolysis. METHODS: Several models were proposed and then simulated with the assistant of Computational fluid dynamics (CFD) framework. The hemolysis performance was calculated using the power law model based on CFD and the estimation model in accordance with geometry parameters proposed in this study. The results of the in vitro experiments were compared with the simulation results. Power law model with the lowest error was utilized in following analysis. RESULTS: As indicated by the simulation result, the rotary speed most significantly affected the hemolysis performance of roller blood pumps, followed by roller number and diameter of tube. The index of hemolysis (IH) for roller blood pumps at a rotary speed of 20-100 rpm ranged from 8.73E-7 to 8.07E-5. The relative error of the estimation model (4.93%) was lower than of the power law model (6.78%). CONCLUSION: The IH led by pumps shows a significant, nonlinear relationship with the rotary speed. The design of multiple rollers design is harmful for hemolysis performance and larger diameter of tube exhibits decreased hemolysis at constant flow rate. An estimation formula was proposed with lower relative error for roller pump with the same shell set, which exhibited reduced computation and elevated convenience. And it can be utilized in hemolysis estimation of roller pumps potentially.
Heart-Assist Devices , Hemolysis , Humans , Equipment Design , Hydrodynamics
Selective endovascular hypothermia has been used to provide cooling-induced cerebral neuroprotection, but current catheters do not support thermally-insulated transfer of cold infusate, which results in an increased exit temperature, causes hemodilution, and limits its cooling efficiency. Herein, air-sprayed fibroin/silica-based coatings combined with chemical vapor deposited parylene-C capping film was prepared on catheter. This coating features in dual-sized-hollow-microparticle incorporated structures with low thermal conductivity. The infusate exit temperature is tunable by adjusting the coating thickness and infusion rate. No peeling or cracking was observed on the coatings under bending and rotational scenarios in the vascular models. Its efficiency was verified in a swine model, and the outlet temperature of coated catheter (75 µm thickness) was 1.8-2.0 °C lower than that of the uncoated one. This pioneering work on catheter thermal insulation coatings may facilitate the clinical translation of selective endovascular hypothermia for neuroprotection in patients with acute ischemic stroke.
Background: The causality between plasma branched-chain amino acids (BCAAs) levels and stroke remains uncertain and the stratified research on the association between BCAAs levels and subtypes of stroke is not well studied. Therefore, the association of genetically proxied circulating BCAA levels with the risks of stroke and its subtypes was explored by Mendelian randomization (MR) in this study. Methods: Summary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses. Data for plasma BCAA levels (n = 16,596) were obtained from a meta-analysis of GWAS. The MEGASTROKE consortium provided data for ischemic stroke (n = 440,328) and its subtypes and data for hemorrhagic stroke were available from 2 meta-analyses of GWAS of European-ancestry groups (intracerebral hemorrhage, n = 3,026; subarachnoid hemorrhage, n = 77,074). The inverse variance weighted (IVW) method was selected as the primary MR analysis. Supplementary analysis used included the weighted median, MR-Egger regression, Cochran's Q statistic, MR Pleiotropy Residual Sum and Outlier global test, and leave-one-out analysis method. Results: According to IVW analysis, 1-SD increment in genetically determined circulating isoleucine was associated with increased risks of cardioembolic stroke (CES) (OR: 1.56, 95% CI: 1.21-2.20, P = 0.0007), but not with risks of other stroke subtypes. We could not discover any proof that leucine and valine levels could increase risk of any stroke subtype. All heterogeneity tests produced stable findings, and there was no concrete evidence to indicate the perturbation of horizontal multiplicity. Conclusion: Increasing plasma isoleucine level had a causal effect on the risk of CES but not on the risk of other stroke subtypes. Further research is needed to identify the mechanisms of the causal associations between BCAAs and stroke subtypes.
INTRODUCTION: The neuroprotection of acute ischemic stroke patients can be achieved by intra-arterial selective cooling infusion using cold saline, which can decrease brain temperature without influencing the body core temperature. This approach can lead to high burdens on the heart and decreased hematocrit in the scenario of loading a high amount of liquid for longtime usage. Therefore, autologous blood is utilized as perfusate to circumvent those side effects. METHODS: In this study, a prototype instrument with an autologous blood cooling system was developed and further evaluated by a mathematical model for brain temperature estimation. RESULTS: Hypothermia could be achieved due to the adequate cooling capacity of the prototype system, which could provide the lowest cooling temperature into the blood vessel of 10.5°C at 25 rpm (209.7 ± 0.8 ml/min). And, the core body temperature did not alter significantly (-0.7 ~ -0.2°C) after 1-h perfusion. The cooling rate and temperature distributions of the brain were analyzed, which showed a 2°C decrease within the initial 5 min infusion by 44 ml/min and 13.7°C perfusate. CONCLUSION: This prototype instrument system could safely cool simulated blood in vitro and reperfuse it to the target cerebral blood vessel. This technique could promote the clinical application of an autologous blood perfusion system for stroke therapy.
Hypothermia, Induced , Ischemic Stroke , Stroke , Body Temperature , Brain , Cold Temperature , Humans , Hypothermia, Induced/methods , Stroke/therapy , Temperature
Intra-arterial selective cooling infusion with the autologous blood (IA-SCAI) is a promising therapeutic hypothermia induction method for conferring neuroprotection to acute ischemic stroke (AIS) patients. The blood heat exchanger (BHE) plays a crucial role in IA-SCAI's cooling capacity. However, there are no BHEs currently available that are specifically designed for the IA-SCAI, which requires a low blood flow to be compatible with cerebral hemodynamics. In an effort to develop a BHE for AIS patients, a prototype of a commercial BHE, Medtronic MYOtherm XP®, was mathematically modeled; specifically, computational fluid dynamics (CFD) was used to analyze its hemo- and thermo-dynamic characteristics under low blood flow including temperature distribution, velocity field and shear stress. Our numerical model predicted the hemolysis index to be 0.0041%-0.0581% inside the BHE with blood flows rates of 10 ml min-1-50 ml min-1. The in vitro heat transfer experiment showed that the BHE efficiently cooled the simulated blood from the initial 37 °C-5.8 °C within 150 s by using cold water (200 ml·min-1, 0 °C). The cooled simulated blood was able to cool the simulated blood in the middle cerebral artery of an artificial circulating system from 37 °C to 16.8 °C-33.7 °C depending on the blood perfusion rate (10-50 ml/min). A biological heat transfer mathematical model showed that brain tissue could be cooled by 2 °C within the initial 1min of infusion. This study verified the feasibility of using a commercial BHE for IA-SCAI and provided insights into its cooling capacity for therapeutic hypothermia.
Hypothermia, Induced , Ischemic Stroke , Body Temperature , Brain/physiology , Hot Temperature , Humans , Hypothermia, Induced/methods , Temperature , Thermodynamics
Intra-arterial selective cooling infusion (IA-SCI) is a promising method for neuroprotection of patients with acute ischemic stroke. One shortcoming of IA-SCI is the elevated delivery temperature caused by the cold perfusate warming along the catheter pathway. Therefore, increasing the thermal resistance of the catheter is of significant importance. In this manuscript, an air-insulated catheter was designed and manufactured through extrusion molding technique. The computational fluid dynamics (CFD)-based thermo-/hemo-dynamics models were exploited to evaluate the thermal conductivity of the catheter. Compared with commercially available endovascular catheters, its thermal insulation property was analyzed through an in vitro experiment. The temperature of the 4°C perfusate (20 ml/min) increased to 14.2°C ± 0.2°C after being transferred to the distal tip of the air-insulated catheter, which was significantly lower than that (30°C) of commercially available alternatives. Moreover, the simulated blood (56% glycerin and 44% bi-distilled water, 37°C) in the middle cerebral artery of the artificial circulating system was cooled down to 29.7°C ± 0.1°C by this perfusate. The cooling process of the brain tissue was also estimated by a biological heat-transfer mathematical model, which showed a 2°C decrease within the initial 1 min infusion. This study demonstrated that the air-insulated catheter for IA-SCI was promising in vitro in terms of its high cooling efficiency and could be a competitive intervention catheter for therapeutic hypothermia.
Brain Ischemia , Hypothermia, Induced , Ischemic Stroke , Brain/blood supply , Catheters , Humans
Over the past two decades, biodegradable metals (BMs) have emerged as promising materials to fabricate temporary biomedical devices, with the purpose of avoiding potential side effects of permanent implants. In this review, we first surveyed the current status of BMs in neuroscience, and briefly summarized the representative stents for treating vascular stenosis. Then, inspired by the convincing clinical evidence on the in vivo safety of Mg alloys as cardiovascular stents, we analyzed the possibility of producing biodegradable cerebrovascular Mg alloy stents for treating ischemic stroke. For these novel applications, some key factors should also be considered in designing BM brain stents, including the anatomic features of the cerebral vasculature, hemodynamic influences, neuro-cytocompatibility and selection of alloying elements. This work may provide insights into the future design and fabrication of BM neurological devices, especially for brain stents.
