The high morbidity and mortality rate of ischemic stroke in humans has led to the development of numerous animal models that replicate human stroke to further understand the underlying pathophysiology and to explore p...The high morbidity and mortality rate of ischemic stroke in humans has led to the development of numerous animal models that replicate human stroke to further understand the underlying pathophysiology and to explore potential therapeutic interventions.Although promising therapeutics have been identified using these animal models,with most undergoing significant testing in rodent models,the vast majority of these interventions have failed in human clinical trials.This failure of preclinical translation highlights the critical need for better therapeutic assessment in more clinically relevant ischemic stroke animal models.Large animal models such as non-human primates,sheep,pigs,and dogs are likely more predictive of human responses and outcomes due to brain anatomy and physiology that are more similar to humans-potentially making large animal testing a key step in the stroke therapy translational pipeline.The objective of this review is to highlight key characteristics that potentially make these gyrencephalic,large animal ischemic stroke models more predictive by comparing pathophysiological responses,tissue-level changes,and model limitations.展开更多
Stroke, including cerebral ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage, is the leading cause of long-term disability and death worldwide. Animal models have greatly contributed to our understanding...Stroke, including cerebral ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage, is the leading cause of long-term disability and death worldwide. Animal models have greatly contributed to our understanding of the risk factors and the pathophysiology of stroke, as well as the development of therapeutic strategies for its treatment. Further development and investigation of experimental models, however, are needed to elucidate the pathogenesis of stroke and to enhance and expand novel therapeutic targets. In this article, we provide an overview of the characteristics of commonly-used animal models of stroke and focus on the inflammatory responses to cerebral stroke, which may provide insights into a framework for developing effective therapies for stroke in humans.展开更多
Because of the aggressive threaten of heat stroke and a lack of understanding of the mechanism of action, mammal animal models for experimental heat stroke were well developed. During the past 5 decades, anesthetized ...Because of the aggressive threaten of heat stroke and a lack of understanding of the mechanism of action, mammal animal models for experimental heat stroke were well developed. During the past 5 decades, anesthetized mouse, rat, rabbit, dog, baboon and monkey were used as animal model for experimental heat stroke. However, anesthetized mammals models have some limitations, such as neuroprotective effect of anesthetic agents, possible disturbance on injury and recovery of stroke animals by anesthetic agents, difficulty of discussing animal behavior before and after heat stroke, it was also difficult for the models to evaluate cognitive function of animal under hot environment. Considering humanitarian, only awaked and unrestrained mouse heat stroke model was accepted so far. Therefore, we also developed an awaked and unrestrained rat heat stroke model, and found it was helpful to evaluate drug effectiveness for animal behavior and cognitive function under hot environment.展开更多
Experimental stroke research commonly employs focal cerebral ischemic rat models （Bederson et al., 1986a; Longa et al., 1989）. In human patients, ischemic stroke typically results from thrombotic or embolic occlusio...Experimental stroke research commonly employs focal cerebral ischemic rat models （Bederson et al., 1986a; Longa et al., 1989）. In human patients, ischemic stroke typically results from thrombotic or embolic occlusion of a major cerebral artery, usually the mid- dle cerebral artery （MCA）. Experimental focal cerebral ischemia models have been employed to mimic human stroke （Durukan and Tatlisumak, 2007）. Rodent models of focal cerebral ischemia that do not require craniotomy have been developed using intraluminal suture occlusion of the MCA （MCA occlusion, MCAO） （Rosamond et al., 2008）. Furthermore, mouse MCAO models have been wide- ly used and extended to genetic studies of cell death or recovery mechanisms （Liu and McCullough, 2011）. Genetically engineered mouse stroke models are particularly useful for evaluation of isch- emic pathophysiology and the design of new prophylactic, neuro- protective, and therapeutic agents and interventions （Armstead et al., 2010）. During the past two decades, MCAO surgical techniques have been developed that do not reveal surgical techniques for mouse MCAO model engineering. Therefore, we compared MCAO surgical methods in rats and mice.展开更多
Stroke is a major health concern and an intensive research subject due that it is the major cause of death and the leading cause of disability worldwide. The past three decades of clinical disappointments in treating ...Stroke is a major health concern and an intensive research subject due that it is the major cause of death and the leading cause of disability worldwide. The past three decades of clinical disappointments in treating stroke must compel us to rethink our strategy. New effective protocol for stroke could greatly benefit from the advances in optical imaging technologies. This review focuses on the latest advance of applications of three optical imaging techniques in animal model of stroke, such as photoacoustic （PA） imaging, laser speckle contrast imaging （LSCI） and two-photon microscopy （TPM）. The potential roles of those techniques in the future of stroke management are also discussed.展开更多
People in the rural areas do not have access to specialist medical care, and when they have complications of stroke, they do not have specialists to look at them and they cannot afford to travel to the cities. The pri...People in the rural areas do not have access to specialist medical care, and when they have complications of stroke, they do not have specialists to look at them and they cannot afford to travel to the cities. The primary health care centers are not equipped with sophisticated equipments. Medicine is about medication, treatment and management. In rural areas treatment is not available either because of accessibility or affordability. Even the few doctors that are available are not in primary health care centres. Well conserved one-dimensional non-linear equations of blood flow describing blood flow in distensible blood vessels were used to develop software. This model could describe discontinuities and disruption in blood flow. The computer software can be used for detecting artherosclerosis, stenosis and differentiation of haemorrhagic and ischaemic strokes for stroke management from simple measurements. The software developed is capable of computing the Siriraj and the Allen clinical scores. These scores have been proposed to help clinicians in making decisions while waiting for results of computerized tomography, hence clinicians can start anti-thrombotic treatment while waiting for the scan results. It is capable of simulating stenosis at different position and depth of flow along the arterial length, and can be used for diagnosis. The medical emphasis is on avoiding possible occurrence, every individual can know his status by inputting the required data such as flow and geometry of their arteries into the developed interface and such measurements can be obtained from simple Doppler measurements.展开更多
We proposed a modified ratchet model including power-stroke and elastic coupling to study the efficiency of collective non-processive motors such as myosin Ⅱ in muscle. Our theoretical results are in good agreement w...We proposed a modified ratchet model including power-stroke and elastic coupling to study the efficiency of collective non-processive motors such as myosin Ⅱ in muscle. Our theoretical results are in good agreement with the experimental data. Our study not only reveals that the maximum efficiency depends on elasticity and is independent of transition rates but also indicates that the parameters fitted to fast muscle are different from those fitted to a slow one. The latter may imply that the structure of the fast muscle is different from that of the slow one. The main reason that our model succeeds is that velocity in this model is an independent variable.展开更多
Objective: To explore nutritional support under the Neuman systems model in treating dysphagia in stroke patients. Methods: In this retrospective study, we enrolled 97 patients with dysphagia after stroke admitted to ...Objective: To explore nutritional support under the Neuman systems model in treating dysphagia in stroke patients. Methods: In this retrospective study, we enrolled 97 patients with dysphagia after stroke admitted to our hospital, and randomly divided them into the Neuman group (n = 51) given nursing intervention based on Neuman systems model and a control group (n = 46) given routine nursing intervention. Both groups received nutritional support for 3 months. Nutritional indexes (serum total protein, plasma albumin, serum albumin, hemoglobin and transferrin levels) and immune indexes (immunoglobulin (Ig) A, IgG, IgM and total lymphocyte count (TLC) in both groups were recorded and compared. Pulmonary function recovery, video fluoroscopic swallowing study score, water swallowing test score, complication rate, and health knowledge mastery level were also compared between the two groups. Results: After the intervention, the Neuman group showed less decrease in the nutritional and immune index scores (serum total protein, plasma albumin, hemoglobin, serum albumin;IgA, IgG, IgM, and TLC;all P Conclusion: For patients with stroke and dysphagia, comprehensive nursing intervention (e.g., nutritional support) under theNeuman systems model can promote the recovery of immune, swallowing, and pulmonary function, reduce complication incidence and facilitate comprehensive rehabilitation, ensuring adequate nutritional intake.展开更多
The links between low temperature and the incidence of disease have been studied by many researchers. What remains still unclear is the exact nature of the relation, especially the mechanism by which the change of wea...The links between low temperature and the incidence of disease have been studied by many researchers. What remains still unclear is the exact nature of the relation, especially the mechanism by which the change of weather effects on the onset of diseases. The existence of lag period between exposure to temperature and its effect on mortality may reflect the nature of the onset of diseases. Therefore, to assess lagged effects becomes potentially important. The most of studies on lags used the method by Lag-distributed Poisson Regression, and neglected extreme case as random noise to get correlations. In order to assess the lagged effect, we proposed a new approach, i.e., Hidden Markov Model by Self Organized Map (HMM by SOM) apart from well-known regression models. HMM by SOM includes the randomness in its nature and encompasses the extreme cases which were neglected by auto-regression models. The daily data of the number of patients transported by ambulance in Nagoya, Japan, were used. SOM was carried out to classify the meteorological elements into six classes. These classes were used as “states” of HMM. HMM was used to describe a background process which might produce the time series of the incidence of diseases. The background process was considered to change randomly weather states, classified by SOM. We estimated the lagged effects of weather change on the onset of both cerebral infarction and ischemic heart disease. This fact is potentially important in that if one could trace a path in the chain of events leading from temperature change to death, one might be able to prevent it and avert the fatal outcome.展开更多
Several studies were devoted to investigate the effects of meteorological factors on the occurrence of stroke. Regression models had been mostly used to assess the correlation between weather and stroke incidence. How...Several studies were devoted to investigate the effects of meteorological factors on the occurrence of stroke. Regression models had been mostly used to assess the correlation between weather and stroke incidence. However, these methods could not describe the process proceeding in the back-ground of stroke incidence. The purpose of this study was to provide a new approach based on Hidden Markov Models (HMMs) and self-organizing maps (SOM), interpreting the background from the viewpoint of weather variability. Based on meteorological data, SOM was performed to classify weather patterns. Using these classes by SOM as randomly changing “states”, our Hidden Markov Models were constructed with “observation data” that were extracted from the daily data of emergency transport at Nagoya City in Japan. We showed that SOM was an effective method to get weather patterns that would serve as “states” of Hidden Markov Models. Our Hidden Markov Models provided effective models to clarify background process for stroke incidence. The effectiveness of these Hidden Markov Models was estimated by stochastic test for root mean square errors (RMSE). “HMMs with states by SOM” would serve as a description of the background process of stroke incidence and were useful to show the influence of weather on stroke onset. This finding will contribute to an improvement of our understanding for links between weather variability and stroke incidence.展开更多
Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. Howe...Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group： middle cerebral artery occlusion at origin segment （M1） and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique （1 mm × 10 cm） （undetachable）, to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research.展开更多
目的探讨急性缺血性脑卒中患者早期铁死亡相关蛋白表达与神经功能恶化和预后的潜在联系。方法选取2020年1月~2022年12月中国人民解放军联勤保障部队第966医院收治的190例发病7天内的急性缺血性卒中患者作为研究对象。入院后24h内采集静...目的探讨急性缺血性脑卒中患者早期铁死亡相关蛋白表达与神经功能恶化和预后的潜在联系。方法选取2020年1月~2022年12月中国人民解放军联勤保障部队第966医院收治的190例发病7天内的急性缺血性卒中患者作为研究对象。入院后24h内采集静脉血样,采用ELISA方法检测血浆中神经丝轻链(NfL)、4-羟基-2-壬烯醛(4-HNE)、8-羟基-2’-脱氧鸟苷(8-oxo-dG)和铁蛋白(Ft)的水平,通过公式计算铁死亡模型评分:-100×NfL+20×4-HNE+17×8-oxo-dG+170×Ft。以卒中发作后3个月的改良Rankin评分(mRS)来评估短期结局,将患者分为预后良好组(mRS≤2,n=136)和预后不良组(mRS≥3,n=54)。比较两组临床特征及铁死亡模型评分的差异,采用Logistic回归分析急性缺血性卒中患者3个月不良结局的影响因素。Spearman相关性分析铁死亡模型评分与美国国立卫生研究院卒中量表(NIHSS)评分的相关性。ROC曲线分析铁死亡模型评分预测急性缺血性卒中患者3个月不良结局的能力。结果与预后良好组相比,预后不良组的4-HNE水平(22.92±4.14ng/ml vs 21.06±2.57ng/ml),8-oxo-dG水平(7.00±1.05ng/ml vs 6.40±0.75ng/ml)和铁死亡模型评分(109.93±11.01 vs 90.44±6.67)均显著升高,NfL水平(91.83±5.20ng/ml vs 93.65±4.74ng/ml)显著降低,差异具有统计学意义(t=2.328~14.906,均P<0.05)。铁死亡模型评分(OR=1.633,95%CI=1.326~2.011)和白蛋白(Alb)(OR=63.266,95%CI=5.581~717.214)是急性缺血性卒中患者3个月不良结局的独立影响因素。相关性分析显示,铁死亡模型评分与入院时NIHSS评分、出院时NIHSS评分呈正相关(r=0.165、0.178,均P<0.05)。当铁死亡模型评分截断值为95.5时,其预测急性缺血性脑卒中患者3个月不良结局的AUC为0.931,敏感度为90.7%,特异度为75.0%。结论铁死亡模型评分与缺血性脑卒中后不良结局相关,并可用于预测患者的短期预后。展开更多
基金supported by the National Institutes of Health,National Institute of Neurological Disorders and Stroke,No.R01NS093314
文摘The high morbidity and mortality rate of ischemic stroke in humans has led to the development of numerous animal models that replicate human stroke to further understand the underlying pathophysiology and to explore potential therapeutic interventions.Although promising therapeutics have been identified using these animal models,with most undergoing significant testing in rodent models,the vast majority of these interventions have failed in human clinical trials.This failure of preclinical translation highlights the critical need for better therapeutic assessment in more clinically relevant ischemic stroke animal models.Large animal models such as non-human primates,sheep,pigs,and dogs are likely more predictive of human responses and outcomes due to brain anatomy and physiology that are more similar to humans-potentially making large animal testing a key step in the stroke therapy translational pipeline.The objective of this review is to highlight key characteristics that potentially make these gyrencephalic,large animal ischemic stroke models more predictive by comparing pathophysiological responses,tissue-level changes,and model limitations.
基金supported by grants from National Institute on Aging (R01 AG031811, R01 AG037506)National Institute of Neurological Disorders and Stroke (R01 NS083078-01A1, R41 NS080329-01A1)+1 种基金American Heart Association grant (14GRNT20460026)the National Natural Science Foundation of China (81300993, 81571145)
文摘Stroke, including cerebral ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage, is the leading cause of long-term disability and death worldwide. Animal models have greatly contributed to our understanding of the risk factors and the pathophysiology of stroke, as well as the development of therapeutic strategies for its treatment. Further development and investigation of experimental models, however, are needed to elucidate the pathogenesis of stroke and to enhance and expand novel therapeutic targets. In this article, we provide an overview of the characteristics of commonly-used animal models of stroke and focus on the inflammatory responses to cerebral stroke, which may provide insights into a framework for developing effective therapies for stroke in humans.
基金supported by grants from National Natural Science Foundation of China(31071042)Chinese Postdoctoral Scientific Foundation(20100480774)
文摘Because of the aggressive threaten of heat stroke and a lack of understanding of the mechanism of action, mammal animal models for experimental heat stroke were well developed. During the past 5 decades, anesthetized mouse, rat, rabbit, dog, baboon and monkey were used as animal model for experimental heat stroke. However, anesthetized mammals models have some limitations, such as neuroprotective effect of anesthetic agents, possible disturbance on injury and recovery of stroke animals by anesthetic agents, difficulty of discussing animal behavior before and after heat stroke, it was also difficult for the models to evaluate cognitive function of animal under hot environment. Considering humanitarian, only awaked and unrestrained mouse heat stroke model was accepted so far. Therefore, we also developed an awaked and unrestrained rat heat stroke model, and found it was helpful to evaluate drug effectiveness for animal behavior and cognitive function under hot environment.
基金supported by the 2013 Inje University Research Grant
文摘Experimental stroke research commonly employs focal cerebral ischemic rat models （Bederson et al., 1986a; Longa et al., 1989）. In human patients, ischemic stroke typically results from thrombotic or embolic occlusion of a major cerebral artery, usually the mid- dle cerebral artery （MCA）. Experimental focal cerebral ischemia models have been employed to mimic human stroke （Durukan and Tatlisumak, 2007）. Rodent models of focal cerebral ischemia that do not require craniotomy have been developed using intraluminal suture occlusion of the MCA （MCA occlusion, MCAO） （Rosamond et al., 2008）. Furthermore, mouse MCAO models have been wide- ly used and extended to genetic studies of cell death or recovery mechanisms （Liu and McCullough, 2011）. Genetically engineered mouse stroke models are particularly useful for evaluation of isch- emic pathophysiology and the design of new prophylactic, neuro- protective, and therapeutic agents and interventions （Armstead et al., 2010）. During the past two decades, MCAO surgical techniques have been developed that do not reveal surgical techniques for mouse MCAO model engineering. Therefore, we compared MCAO surgical methods in rats and mice.
文摘Stroke is a major health concern and an intensive research subject due that it is the major cause of death and the leading cause of disability worldwide. The past three decades of clinical disappointments in treating stroke must compel us to rethink our strategy. New effective protocol for stroke could greatly benefit from the advances in optical imaging technologies. This review focuses on the latest advance of applications of three optical imaging techniques in animal model of stroke, such as photoacoustic （PA） imaging, laser speckle contrast imaging （LSCI） and two-photon microscopy （TPM）. The potential roles of those techniques in the future of stroke management are also discussed.
文摘People in the rural areas do not have access to specialist medical care, and when they have complications of stroke, they do not have specialists to look at them and they cannot afford to travel to the cities. The primary health care centers are not equipped with sophisticated equipments. Medicine is about medication, treatment and management. In rural areas treatment is not available either because of accessibility or affordability. Even the few doctors that are available are not in primary health care centres. Well conserved one-dimensional non-linear equations of blood flow describing blood flow in distensible blood vessels were used to develop software. This model could describe discontinuities and disruption in blood flow. The computer software can be used for detecting artherosclerosis, stenosis and differentiation of haemorrhagic and ischaemic strokes for stroke management from simple measurements. The software developed is capable of computing the Siriraj and the Allen clinical scores. These scores have been proposed to help clinicians in making decisions while waiting for results of computerized tomography, hence clinicians can start anti-thrombotic treatment while waiting for the scan results. It is capable of simulating stenosis at different position and depth of flow along the arterial length, and can be used for diagnosis. The medical emphasis is on avoiding possible occurrence, every individual can know his status by inputting the required data such as flow and geometry of their arteries into the developed interface and such measurements can be obtained from simple Doppler measurements.
基金Project supported by the Key Research Program of Frontier Sciences of Chinese Academy of Sciences(Grant No.Y7Y1472Y61)the National Natural Science Foundation of China(Grant Nos.11205123,11574329,11774358,11747601,and 11675017)+3 种基金the Joint NSFC–ISF Research Program(Grant No.51561145002)the CAS Biophysics Interdisciplinary Innovation Team Project(Grant No.2060299)the CAS Strategic Priority Research Program(Grant No.XDA17010504)the Fundamental Research Funds for the Central Universities(Grant No.2017EYT24)
文摘We proposed a modified ratchet model including power-stroke and elastic coupling to study the efficiency of collective non-processive motors such as myosin Ⅱ in muscle. Our theoretical results are in good agreement with the experimental data. Our study not only reveals that the maximum efficiency depends on elasticity and is independent of transition rates but also indicates that the parameters fitted to fast muscle are different from those fitted to a slow one. The latter may imply that the structure of the fast muscle is different from that of the slow one. The main reason that our model succeeds is that velocity in this model is an independent variable.
文摘Objective: To explore nutritional support under the Neuman systems model in treating dysphagia in stroke patients. Methods: In this retrospective study, we enrolled 97 patients with dysphagia after stroke admitted to our hospital, and randomly divided them into the Neuman group (n = 51) given nursing intervention based on Neuman systems model and a control group (n = 46) given routine nursing intervention. Both groups received nutritional support for 3 months. Nutritional indexes (serum total protein, plasma albumin, serum albumin, hemoglobin and transferrin levels) and immune indexes (immunoglobulin (Ig) A, IgG, IgM and total lymphocyte count (TLC) in both groups were recorded and compared. Pulmonary function recovery, video fluoroscopic swallowing study score, water swallowing test score, complication rate, and health knowledge mastery level were also compared between the two groups. Results: After the intervention, the Neuman group showed less decrease in the nutritional and immune index scores (serum total protein, plasma albumin, hemoglobin, serum albumin;IgA, IgG, IgM, and TLC;all P Conclusion: For patients with stroke and dysphagia, comprehensive nursing intervention (e.g., nutritional support) under theNeuman systems model can promote the recovery of immune, swallowing, and pulmonary function, reduce complication incidence and facilitate comprehensive rehabilitation, ensuring adequate nutritional intake.
文摘The links between low temperature and the incidence of disease have been studied by many researchers. What remains still unclear is the exact nature of the relation, especially the mechanism by which the change of weather effects on the onset of diseases. The existence of lag period between exposure to temperature and its effect on mortality may reflect the nature of the onset of diseases. Therefore, to assess lagged effects becomes potentially important. The most of studies on lags used the method by Lag-distributed Poisson Regression, and neglected extreme case as random noise to get correlations. In order to assess the lagged effect, we proposed a new approach, i.e., Hidden Markov Model by Self Organized Map (HMM by SOM) apart from well-known regression models. HMM by SOM includes the randomness in its nature and encompasses the extreme cases which were neglected by auto-regression models. The daily data of the number of patients transported by ambulance in Nagoya, Japan, were used. SOM was carried out to classify the meteorological elements into six classes. These classes were used as “states” of HMM. HMM was used to describe a background process which might produce the time series of the incidence of diseases. The background process was considered to change randomly weather states, classified by SOM. We estimated the lagged effects of weather change on the onset of both cerebral infarction and ischemic heart disease. This fact is potentially important in that if one could trace a path in the chain of events leading from temperature change to death, one might be able to prevent it and avert the fatal outcome.
文摘Several studies were devoted to investigate the effects of meteorological factors on the occurrence of stroke. Regression models had been mostly used to assess the correlation between weather and stroke incidence. However, these methods could not describe the process proceeding in the back-ground of stroke incidence. The purpose of this study was to provide a new approach based on Hidden Markov Models (HMMs) and self-organizing maps (SOM), interpreting the background from the viewpoint of weather variability. Based on meteorological data, SOM was performed to classify weather patterns. Using these classes by SOM as randomly changing “states”, our Hidden Markov Models were constructed with “observation data” that were extracted from the daily data of emergency transport at Nagoya City in Japan. We showed that SOM was an effective method to get weather patterns that would serve as “states” of Hidden Markov Models. Our Hidden Markov Models provided effective models to clarify background process for stroke incidence. The effectiveness of these Hidden Markov Models was estimated by stochastic test for root mean square errors (RMSE). “HMMs with states by SOM” would serve as a description of the background process of stroke incidence and were useful to show the influence of weather on stroke onset. This finding will contribute to an improvement of our understanding for links between weather variability and stroke incidence.
基金supported by grants from the National Key Basic Research Program(973 Program)of China,No.2011CB707804Beijing Municipal Science and Technology Project,No.2121100005312016
文摘Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group： middle cerebral artery occlusion at origin segment （M1） and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique （1 mm × 10 cm） （undetachable）, to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research.
文摘目的探讨急性缺血性脑卒中患者早期铁死亡相关蛋白表达与神经功能恶化和预后的潜在联系。方法选取2020年1月~2022年12月中国人民解放军联勤保障部队第966医院收治的190例发病7天内的急性缺血性卒中患者作为研究对象。入院后24h内采集静脉血样,采用ELISA方法检测血浆中神经丝轻链(NfL)、4-羟基-2-壬烯醛(4-HNE)、8-羟基-2’-脱氧鸟苷(8-oxo-dG)和铁蛋白(Ft)的水平,通过公式计算铁死亡模型评分:-100×NfL+20×4-HNE+17×8-oxo-dG+170×Ft。以卒中发作后3个月的改良Rankin评分(mRS)来评估短期结局,将患者分为预后良好组(mRS≤2,n=136)和预后不良组(mRS≥3,n=54)。比较两组临床特征及铁死亡模型评分的差异,采用Logistic回归分析急性缺血性卒中患者3个月不良结局的影响因素。Spearman相关性分析铁死亡模型评分与美国国立卫生研究院卒中量表(NIHSS)评分的相关性。ROC曲线分析铁死亡模型评分预测急性缺血性卒中患者3个月不良结局的能力。结果与预后良好组相比,预后不良组的4-HNE水平(22.92±4.14ng/ml vs 21.06±2.57ng/ml),8-oxo-dG水平(7.00±1.05ng/ml vs 6.40±0.75ng/ml)和铁死亡模型评分(109.93±11.01 vs 90.44±6.67)均显著升高,NfL水平(91.83±5.20ng/ml vs 93.65±4.74ng/ml)显著降低,差异具有统计学意义(t=2.328~14.906,均P<0.05)。铁死亡模型评分(OR=1.633,95%CI=1.326~2.011)和白蛋白(Alb)(OR=63.266,95%CI=5.581~717.214)是急性缺血性卒中患者3个月不良结局的独立影响因素。相关性分析显示,铁死亡模型评分与入院时NIHSS评分、出院时NIHSS评分呈正相关(r=0.165、0.178,均P<0.05)。当铁死亡模型评分截断值为95.5时,其预测急性缺血性脑卒中患者3个月不良结局的AUC为0.931,敏感度为90.7%,特异度为75.0%。结论铁死亡模型评分与缺血性脑卒中后不良结局相关,并可用于预测患者的短期预后。
