The current animal models of stroke primarily model a single intracerebral hemorrhage(ICH)attack,and there is a lack of a reliable model of recurrent ICH.In this study,we established 16-month-old C57 B L/6 male mouse ...The current animal models of stroke primarily model a single intracerebral hemorrhage(ICH)attack,and there is a lack of a reliable model of recurrent ICH.In this study,we established 16-month-old C57 B L/6 male mouse models of ICH by injecting collagenaseⅦ-S into the left striatum.Twenty-one days later,we injected collagenaseⅦ-S into the right striatum to simulate recurrent ICH.Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage,delayed recovery in locomotor function,motor coordination,and movement speed,and more obvious emotional and cognitive dysfunction than mice subjected to unilate ral striatal hemorrhage.These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH.These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.展开更多
BACKGROUND ： Experimental animal models of intracerebral hemorrhag （ICH） are greatly needed, so the process of establishment should be ideal in hematoma formation and easy to operate. OBJECTIVE ： To construct mode...BACKGROUND ： Experimental animal models of intracerebral hemorrhag （ICH） are greatly needed, so the process of establishment should be ideal in hematoma formation and easy to operate. OBJECTIVE ： To construct model of ICH in rats with double injection of autologous blood taken from the cut tail cut and double withdrawal of the needle （shortened as two-step injection model）, and compare with those induced by single and double injections. DESIGN ： A randomized controlled tria SETTING： Department of Neurology, General Hospital of Military Area Command of Chinese PLA. MATERIALS： Thirty male Wistar rats of 10 to 12 months, weighing （400±25） g, provided by the Experimental Center of Medical Animals, General Hospital of Shenyang Military Area Command of Chinese PLA, were divided randomly into 3 groups with 10 rats in each group： two-step injection group, single injection group, double injection group. METHODS ： The experiment was carried out in the Department of Neurology, General Hospital of Military Area Command of Chinese PLA from March to June in 2004. Autologous blood ICH model in rats were established as follows： In the two-step injection group, 50 μL unclotted autologous blood was taken from the rat tail cut, then injected with microsyringe into the caudate nucleus, 10 μL injected at first, paused for 2 minutes, and then the rest 40 μL injected slowly and continuously within 2 minutes. After the injection, the needle was kept immovable for about 4 minutes, withdrawn 2.0 mm, again kept immovable for about 4 minute, and then removed wholly at a slow speed. In the single injection group, 50 μL unclotted tail blood was injected slowly and continuously all within 2 minutes and the needle was slowly removed;（4） In the double injection group, 10 mL blood was injected at first, paused for 2 minutes, the rest 40 μL injected evenly within 2 minutes, and then the needle was withdrawn slowly and uninterruptedly. Neurologic findings were scored in accordance with Longa＇s five-point scale （0-4 scores, the higher the score, the severer the neurological dysfunction）. The rats were killed to remove and sections were prepared, the morphological features of hematomas were grossly observed, the maximal diameter and size of hematomas in each slice were measured with the imaging analytical system, and the volume was calculated. Meanwhile, the conveniences of the techniques were compared. MAIN OUTCOME MEASURES： The morphological features and volume of hematomas, neurologic deficit score （NDS）, and the convenience of the techniques were compared. RESULTS： All the 30 rats were involved in the analysis of results without deletion. （1） Results of the morphological observation of volume of hematoma： In the two-step injection group, hematomas located in the right caudate nucleus area regularly in circular or analogously circular shape in each slice. The formation rate of hematomas in the single injection group and double injection group were lower than those in the two-step injection group [60% （6/10）, 80% （8/10）, 100% （10/10）, P〈 0.01, 0.05]. The volume of hematomas in the single injection group and double injection group were smaller than those in the two-step injection group [（28.5±14.8）, （33.4±7.4）, （41.6±3.9） mm3, P〈 0.01, 0.05]. （2） NDS results： The NDS scores in the single injection group and double injection group were smaller than that in the two-step injection group （0.90±0.83, 1.30±0.78, 1.90±0.57, P〈 0.05）. （3）Comparison of the convenience of the techniques： The double injection method allowed generating reproducible hematomas in rats with shortcomings that it needed autologous arterial blood from femoral artery, and precision instruments such as microinfusion pump. The two-step injection injected fresh unclotting blood taken directly from the tail cut with microsyringe into the rat brain, and it has the advantages of easy operation, no influence on the activity of thrombase, shorter duration for model establishment, and higher rate of hematoma formation, which could generate ideal and economical models of ICH. The two-step injection induced hemotoma regularly in circular or analogously circular shape in each slice, but those induced by single and double injections were mostly in strip or fusiform shapes and extending along the needle tracks or into the ventricle or subarachnoid space. CONCLUSION ： The autologous blood ICH model induced by the two-step injection method is a reproducible and reliable one in regular shape, which is better than those induced by double and single injections.展开更多
Background:Severe intracerebral hemorrhage(ICH)is the most devastating subtype of stroke resulting in high mortality and disability.At present,the development of targeted treatments to minimize the high morbidity and ...Background:Severe intracerebral hemorrhage(ICH)is the most devastating subtype of stroke resulting in high mortality and disability.At present,the development of targeted treatments to minimize the high morbidity and mortality is limited partly due to the lack of a severe ICH animal model.In this study,we aimed to establish an accurate severe ICH model in rats and examine the pathological and physiological changes associated with ICH.Methods:A rat model of severe ICH model was established by intrastriatal injection of autologous blood using different blood volumes(ICH 100μL group,ICH 130μL group,ICH 160μL group,ICH 170μL group,and ICH 180μL group).The mortality was assessed during the 28-day post-ICH period.Short-and long-term neurological deficits were evaluated using the Longa method,foot fault,falling latency,and Morris water maze tests.Brain water content,hematoma volume,hemoglobin content,and magnetic resonance imaging were assessed to determine the extent of brain injury.Immunofluorescence staining was conducted to examine microglial activation and neuronal apoptosis.Hematoxylin and eosin(H&E)staining,lung water content,and western blotting were used to assess lung injury following ICH.Results:The mortality of ICH rats increased significantly with an increase in autologous blood injection.The 28-day mortality in the 100μL,130μL,160μL,170μL,and 180μL ICH groups were 5%,20%,40%,75%,and 100%,respectively.A significantly higher 28-day mortality was observed in the ICH 160μL group compared to the ICH 100μL group.The ICH 160μL group exhibited significantly increased neurological deficits,brain edema,hematoma volume,and hemoglobin content compared to the sham group.Compared with the sham operation group,the activation of microglia and neuronal death in ICH 160μL rats increased.The use of H&E staining and western blotting demonstrated that disruption of the intra-alveolar structure,alveolar edema,and infiltration of inflammatory cells and cytokines into the lung tissue were more severe in the ICH 160μL group than the sham group.Conclusions:A severe ICH model in rats was successfully established using an injection of autologous blood at a volume of 160μL.This model may provide a valuable tool to examine the pathological mechanisms and potential therapeutic interventions of severe ICH.展开更多
There is no effective treatment for hemiplegia after hypertensive intracerebral hemorrhage.Considering that the branches of L4 nerve roots in the lumbar plexus root control the movement of the lower extremity anterior...There is no effective treatment for hemiplegia after hypertensive intracerebral hemorrhage.Considering that the branches of L4 nerve roots in the lumbar plexus root control the movement of the lower extremity anterior and posterior muscles,we investigated a potential method of nerve repair using the L4 nerve roots.Rat models of hindlimb hemiplegia after a hypertensive intracerebral hemorrhage were established by injecting autogenous blood into the posterior limb of internal capsule.The L4 nerve root on the healthy side of model rats was transferred and then anastomosed with the L4 nerve root on the affected side to drive the extensor and flexor muscles of the hindlimbs.We investigated whether this method can restore the flexible movement of the hindlimbs of paralyzed rats after hypertensive intracerebral hemorrhage.In a beam-walking test and ladder rung walking task,model rats exhibited an initial high number of slips,but improved in accuracy on the paretic side over time.At 17 weeks after surgery,rats gained approximately 58.2%accuracy from baseline performance and performed ankle motions on the paretic side.At 9 weeks after surgery,a retrograde tracing test showed a large number of fluoro-gold-labeled motoneurons in the left anterior horn of the spinal cord that supports the L4-to-L4 nerve roots.In addition,histological and ultramicrostructural findings showed axon regeneration of motoneurons in the anterior horn of the spinal cord.Electromyography and paw print analysis showed that denervated hindlimb muscles regained reliable innervation and walking coordination improved.These findings suggest that the L4-to-L4 nerve root transfer method for the treatment of hindlimb hemiplegia after hypertensive intracerebral hemorrhage can improve the locomotion of hindlimb major joints,particularly of the distal ankle.Findings from study support that the L4-to-L4 nerve root transfer method can effectively repair the hindlimb hemiplegia after hypertensive intracerebral hemorrhage.All animal experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Nanjing Medical University(No.IACUC-1906009)in June 2019.展开更多
Microwave technology offers the possibility for pre-hospital stroke detection as we have previously demonstrated using non-imaging diagnostics. The focus in this paper is on image-based diagnostics wherein the technic...Microwave technology offers the possibility for pre-hospital stroke detection as we have previously demonstrated using non-imaging diagnostics. The focus in this paper is on image-based diagnostics wherein the technical and computational complexities of image reconstruction are a challenge for clinical realization. Herein we investigate whether information about a patient’s brain anatomy obtained prior to a stroke event can be used to facilitate image-based stroke diagnostics. A priori information can be obtained by segmenting the patient’s head tissues from magnetic resonance images. Expert manual segmentation is presently the gold standard, but it is laborious and subjective. A fully automatic method is thus desirable. This paper presents an evaluation of several such methods using both synthetic magnetic resonance imaging (MRI) data and real data from four healthy subjects. The segmentation was performed on the full 3D MRI data, whereas the electromagnetic evaluation was performed using a 2D slice. The methods were evaluated in terms of: i) tissue classification accuracy over all tissues with respect to ground truth, ii) the accuracy of the simulated electromagnetic wave propagation through the head, and iii) the accuracy of the image reconstruction of the hemorrhage. The segmentation accuracy was measured in terms of the degree of overlap (Dice score) with the ground truth. The electromagnetic simulation accuracy was measured in terms of signal deviation relative to the simulation based on the ground truth. Finally, the image reconstruction accuracy was measured in terms of the Dice score, relative error of dielectric properties, and visual comparison between the true and reconstructed intracerebral hemorrhage. The results show that accurate segmentation of tissues (Dice score = 0.97) from the MRI data can lead to accurate image reconstruction (relative error = 0.24) for the intracerebral hemorrhage in the subject’s brain. They also suggest that accurate automated segmentation can be used as a surrogate for manual segmentation and can facilitate the rapid diagnosis of intracerebral hemorrhage in stroke patients using a microwave imaging system.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
Stroke is a devastating disease with high morbidity and mortality.Animal models are indispensable tools that can mimic stroke processes and can be used for investigating mechanisms and developing novel therapeutic reg...Stroke is a devastating disease with high morbidity and mortality.Animal models are indispensable tools that can mimic stroke processes and can be used for investigating mechanisms and developing novel therapeutic regimens.As a heterogeneous disease with complex pathophysiology,mimicking all aspects of human stroke in one animal model is impossible.Each model has unique strengths and weaknesses.Models such as transient or permanent intraluminal thread occlusion middle cerebral artery oc-clusion(MCAo)models and thromboembolic models are the most commonly used in simulating human ischemic stroke.The endovascular filament occlusion model is characterized by easy manipulation and accurately controllable reperfusion and is suitable for studying the pathogenesis of focal ischemic stroke and reperfusion in-jury.Although the reproducibility of the embolic model is poor,it is more conveni-ent for investigating thrombolysis.Rats are the most frequently used animal model for stroke.This review mainly outlines the stroke models of rats and discusses their strengths and shortcomings in detail.展开更多
目的探究阿托伐他汀对高血糖诱导的小鼠脑缺血后出血转化(HT)的作用及机制。方法36只SPF级雄性C57BL/6小鼠随机分为假手术组、HT模型组和阿托伐他汀组,每组12只。比较各组小鼠神经功能评分、死亡率、HT发生率、HT分级评分,苏木精-伊红...目的探究阿托伐他汀对高血糖诱导的小鼠脑缺血后出血转化(HT)的作用及机制。方法36只SPF级雄性C57BL/6小鼠随机分为假手术组、HT模型组和阿托伐他汀组,每组12只。比较各组小鼠神经功能评分、死亡率、HT发生率、HT分级评分,苏木精-伊红染色观察脑组织出血情况,免疫荧光染色评估血脑屏障通透性,Western blot检测缺血半暗带脑组织免疫球蛋白G(IgG)、闭锁连接蛋白1(ZO-1)、闭合蛋白(occludin)、紧密连接蛋白5(claudin5)、基质金属蛋白酶(MMP)2和MMP-9的蛋白表达。结果与假手术组比较,HT模型组神经功能评分、死亡率、HT发生率、HT评分、IgG荧光强度、IgG、MMP-2、MMP-9蛋白表达水平显著增高,ZO-1、occludin、claudin5蛋白表达水平明显降低(P<0.01)。与HT模型组比较,阿托伐他汀组神经功能评分、死亡率、HT发生率、HT评分、IgG荧光强度及IgG、MMP-2、MMP-9蛋白表达水平显著降低[(2.73±1.19)分vs(3.91±0.94)分,16.7%vs 41.6%,58.3%vs 91.6%,(1.00±1.04)分vs(2.58±1.13)分,(504.30±105.52)a.u vs(859.91±153.28)a.u,4.55±1.40 vs 12.06±3.73,1.87±0.41 vs 2.95±0.68,1.47±0.24 vs 2.12±0.23,P<0.05,P<0.01],ZO-1、occludin、claduin5蛋白表达显著升高(1.55±0.20 vs 0.53±0.10,0.92±0.11 vs 0.35±0.07、0.58±0.04 vs 0.30±0.05,P<0.01)。结论阿托伐他汀可通过抑制MMP-2、MMP-9激活,上调ZO-1、occludin、claudin5表达,降低血脑屏障通透性,从而抑制高血糖诱导的脑缺血后HT。展开更多
目的系统评价急性缺血性卒中静脉溶栓后症状性颅内出血预测模型的特征,为静脉溶栓临床决策提供参考。方法检索中国知网、万方数据知识服务平台、维普资讯、PubMed、Embase、Web of Science和The Cochrane Library数据库,收集急性缺血性...目的系统评价急性缺血性卒中静脉溶栓后症状性颅内出血预测模型的特征,为静脉溶栓临床决策提供参考。方法检索中国知网、万方数据知识服务平台、维普资讯、PubMed、Embase、Web of Science和The Cochrane Library数据库,收集急性缺血性卒中静脉溶栓后症状性颅内出血预测模型相关研究信息,检索时限为建库至2022年12月18日。由2位研究员独立筛选文献、提取资料并评价偏倚风险后对纳入模型的基本特征和方法论进行系统评价。结果纳入20项研究,共30个预测模型。纳入模型ROC曲线的AUC值范围为0.42~0.94。24个(80%)预测模型的整体预测性能较好,模型对不同结局的定义和算法的区分度有明显差异。最常见的预测因子包括NIHSS评分、年龄、梗死的影像学征象或评分、血糖、收缩压和抗血小板药物。结论急性缺血性卒中静脉溶栓后症状性颅内出血预测模型呈现出建模算法多样化、模型性能更佳化、预测因素多元化等特点,但总体偏倚风险较高,未来研究还需要进一步校准模型。此外,应更加关注模型的更新与外部验证,提高其外推性及临床效用,从而发挥模型更大的临床价值。展开更多
基金supported by the Natural Science Foundation of Guangdong Province of China,No.2018A030313427the Science and Technology Program of Guangzhou of China,No.202002030393(both to LMW)。
文摘The current animal models of stroke primarily model a single intracerebral hemorrhage(ICH)attack,and there is a lack of a reliable model of recurrent ICH.In this study,we established 16-month-old C57 B L/6 male mouse models of ICH by injecting collagenaseⅦ-S into the left striatum.Twenty-one days later,we injected collagenaseⅦ-S into the right striatum to simulate recurrent ICH.Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage,delayed recovery in locomotor function,motor coordination,and movement speed,and more obvious emotional and cognitive dysfunction than mice subjected to unilate ral striatal hemorrhage.These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH.These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.
文摘BACKGROUND ： Experimental animal models of intracerebral hemorrhag （ICH） are greatly needed, so the process of establishment should be ideal in hematoma formation and easy to operate. OBJECTIVE ： To construct model of ICH in rats with double injection of autologous blood taken from the cut tail cut and double withdrawal of the needle （shortened as two-step injection model）, and compare with those induced by single and double injections. DESIGN ： A randomized controlled tria SETTING： Department of Neurology, General Hospital of Military Area Command of Chinese PLA. MATERIALS： Thirty male Wistar rats of 10 to 12 months, weighing （400±25） g, provided by the Experimental Center of Medical Animals, General Hospital of Shenyang Military Area Command of Chinese PLA, were divided randomly into 3 groups with 10 rats in each group： two-step injection group, single injection group, double injection group. METHODS ： The experiment was carried out in the Department of Neurology, General Hospital of Military Area Command of Chinese PLA from March to June in 2004. Autologous blood ICH model in rats were established as follows： In the two-step injection group, 50 μL unclotted autologous blood was taken from the rat tail cut, then injected with microsyringe into the caudate nucleus, 10 μL injected at first, paused for 2 minutes, and then the rest 40 μL injected slowly and continuously within 2 minutes. After the injection, the needle was kept immovable for about 4 minutes, withdrawn 2.0 mm, again kept immovable for about 4 minute, and then removed wholly at a slow speed. In the single injection group, 50 μL unclotted tail blood was injected slowly and continuously all within 2 minutes and the needle was slowly removed;（4） In the double injection group, 10 mL blood was injected at first, paused for 2 minutes, the rest 40 μL injected evenly within 2 minutes, and then the needle was withdrawn slowly and uninterruptedly. Neurologic findings were scored in accordance with Longa＇s five-point scale （0-4 scores, the higher the score, the severer the neurological dysfunction）. The rats were killed to remove and sections were prepared, the morphological features of hematomas were grossly observed, the maximal diameter and size of hematomas in each slice were measured with the imaging analytical system, and the volume was calculated. Meanwhile, the conveniences of the techniques were compared. MAIN OUTCOME MEASURES： The morphological features and volume of hematomas, neurologic deficit score （NDS）, and the convenience of the techniques were compared. RESULTS： All the 30 rats were involved in the analysis of results without deletion. （1） Results of the morphological observation of volume of hematoma： In the two-step injection group, hematomas located in the right caudate nucleus area regularly in circular or analogously circular shape in each slice. The formation rate of hematomas in the single injection group and double injection group were lower than those in the two-step injection group [60% （6/10）, 80% （8/10）, 100% （10/10）, P〈 0.01, 0.05]. The volume of hematomas in the single injection group and double injection group were smaller than those in the two-step injection group [（28.5±14.8）, （33.4±7.4）, （41.6±3.9） mm3, P〈 0.01, 0.05]. （2） NDS results： The NDS scores in the single injection group and double injection group were smaller than that in the two-step injection group （0.90±0.83, 1.30±0.78, 1.90±0.57, P〈 0.05）. （3）Comparison of the convenience of the techniques： The double injection method allowed generating reproducible hematomas in rats with shortcomings that it needed autologous arterial blood from femoral artery, and precision instruments such as microinfusion pump. The two-step injection injected fresh unclotting blood taken directly from the tail cut with microsyringe into the rat brain, and it has the advantages of easy operation, no influence on the activity of thrombase, shorter duration for model establishment, and higher rate of hematoma formation, which could generate ideal and economical models of ICH. The two-step injection induced hemotoma regularly in circular or analogously circular shape in each slice, but those induced by single and double injections were mostly in strip or fusiform shapes and extending along the needle tracks or into the ventricle or subarachnoid space. CONCLUSION ： The autologous blood ICH model induced by the two-step injection method is a reproducible and reliable one in regular shape, which is better than those induced by double and single injections.
基金supported by a grant from the Shanghai Hospital Development Center(SHDC2020CR3021A to YG)the Science and Technology Commission of Shanghai Municipality(21ZR1410700 to S.D.)the National Natural Science Foun-dation of China(82101536 to S.D.).
文摘Background:Severe intracerebral hemorrhage(ICH)is the most devastating subtype of stroke resulting in high mortality and disability.At present,the development of targeted treatments to minimize the high morbidity and mortality is limited partly due to the lack of a severe ICH animal model.In this study,we aimed to establish an accurate severe ICH model in rats and examine the pathological and physiological changes associated with ICH.Methods:A rat model of severe ICH model was established by intrastriatal injection of autologous blood using different blood volumes(ICH 100μL group,ICH 130μL group,ICH 160μL group,ICH 170μL group,and ICH 180μL group).The mortality was assessed during the 28-day post-ICH period.Short-and long-term neurological deficits were evaluated using the Longa method,foot fault,falling latency,and Morris water maze tests.Brain water content,hematoma volume,hemoglobin content,and magnetic resonance imaging were assessed to determine the extent of brain injury.Immunofluorescence staining was conducted to examine microglial activation and neuronal apoptosis.Hematoxylin and eosin(H&E)staining,lung water content,and western blotting were used to assess lung injury following ICH.Results:The mortality of ICH rats increased significantly with an increase in autologous blood injection.The 28-day mortality in the 100μL,130μL,160μL,170μL,and 180μL ICH groups were 5%,20%,40%,75%,and 100%,respectively.A significantly higher 28-day mortality was observed in the ICH 160μL group compared to the ICH 100μL group.The ICH 160μL group exhibited significantly increased neurological deficits,brain edema,hematoma volume,and hemoglobin content compared to the sham group.Compared with the sham operation group,the activation of microglia and neuronal death in ICH 160μL rats increased.The use of H&E staining and western blotting demonstrated that disruption of the intra-alveolar structure,alveolar edema,and infiltration of inflammatory cells and cytokines into the lung tissue were more severe in the ICH 160μL group than the sham group.Conclusions:A severe ICH model in rats was successfully established using an injection of autologous blood at a volume of 160μL.This model may provide a valuable tool to examine the pathological mechanisms and potential therapeutic interventions of severe ICH.
基金the National Natural Science Foundation of China,No.81171147(to LXL)“Key Medical Talents of Qiangwei Project”Research Foundation of Health Department of Jiangsu Province,No.ZDRCA2016010(to LXL)+3 种基金“Xingwei Project”Key Personal Medical Research Foundation of Health Department of Jiangsu Province,No.RC201156(to LXL)Jiangsu Province’s Key Discipline of Medicine,No.XK201117(to LXL)the Priority Academic Program Development of Jiangsu Higher Education Institutions,PAPD(to LXL)the Natural Science Foundation of Jiangsu Province,No.BK20171064(to BSH).
文摘There is no effective treatment for hemiplegia after hypertensive intracerebral hemorrhage.Considering that the branches of L4 nerve roots in the lumbar plexus root control the movement of the lower extremity anterior and posterior muscles,we investigated a potential method of nerve repair using the L4 nerve roots.Rat models of hindlimb hemiplegia after a hypertensive intracerebral hemorrhage were established by injecting autogenous blood into the posterior limb of internal capsule.The L4 nerve root on the healthy side of model rats was transferred and then anastomosed with the L4 nerve root on the affected side to drive the extensor and flexor muscles of the hindlimbs.We investigated whether this method can restore the flexible movement of the hindlimbs of paralyzed rats after hypertensive intracerebral hemorrhage.In a beam-walking test and ladder rung walking task,model rats exhibited an initial high number of slips,but improved in accuracy on the paretic side over time.At 17 weeks after surgery,rats gained approximately 58.2%accuracy from baseline performance and performed ankle motions on the paretic side.At 9 weeks after surgery,a retrograde tracing test showed a large number of fluoro-gold-labeled motoneurons in the left anterior horn of the spinal cord that supports the L4-to-L4 nerve roots.In addition,histological and ultramicrostructural findings showed axon regeneration of motoneurons in the anterior horn of the spinal cord.Electromyography and paw print analysis showed that denervated hindlimb muscles regained reliable innervation and walking coordination improved.These findings suggest that the L4-to-L4 nerve root transfer method for the treatment of hindlimb hemiplegia after hypertensive intracerebral hemorrhage can improve the locomotion of hindlimb major joints,particularly of the distal ankle.Findings from study support that the L4-to-L4 nerve root transfer method can effectively repair the hindlimb hemiplegia after hypertensive intracerebral hemorrhage.All animal experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Nanjing Medical University(No.IACUC-1906009)in June 2019.
文摘Microwave technology offers the possibility for pre-hospital stroke detection as we have previously demonstrated using non-imaging diagnostics. The focus in this paper is on image-based diagnostics wherein the technical and computational complexities of image reconstruction are a challenge for clinical realization. Herein we investigate whether information about a patient’s brain anatomy obtained prior to a stroke event can be used to facilitate image-based stroke diagnostics. A priori information can be obtained by segmenting the patient’s head tissues from magnetic resonance images. Expert manual segmentation is presently the gold standard, but it is laborious and subjective. A fully automatic method is thus desirable. This paper presents an evaluation of several such methods using both synthetic magnetic resonance imaging (MRI) data and real data from four healthy subjects. The segmentation was performed on the full 3D MRI data, whereas the electromagnetic evaluation was performed using a 2D slice. The methods were evaluated in terms of: i) tissue classification accuracy over all tissues with respect to ground truth, ii) the accuracy of the simulated electromagnetic wave propagation through the head, and iii) the accuracy of the image reconstruction of the hemorrhage. The segmentation accuracy was measured in terms of the degree of overlap (Dice score) with the ground truth. The electromagnetic simulation accuracy was measured in terms of signal deviation relative to the simulation based on the ground truth. Finally, the image reconstruction accuracy was measured in terms of the Dice score, relative error of dielectric properties, and visual comparison between the true and reconstructed intracerebral hemorrhage. The results show that accurate segmentation of tissues (Dice score = 0.97) from the MRI data can lead to accurate image reconstruction (relative error = 0.24) for the intracerebral hemorrhage in the subject’s brain. They also suggest that accurate automated segmentation can be used as a surrogate for manual segmentation and can facilitate the rapid diagnosis of intracerebral hemorrhage in stroke patients using a microwave imaging system.
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National Natural Science Foundation of China,Grant/Award Number:31970777。
文摘Stroke is a devastating disease with high morbidity and mortality.Animal models are indispensable tools that can mimic stroke processes and can be used for investigating mechanisms and developing novel therapeutic regimens.As a heterogeneous disease with complex pathophysiology,mimicking all aspects of human stroke in one animal model is impossible.Each model has unique strengths and weaknesses.Models such as transient or permanent intraluminal thread occlusion middle cerebral artery oc-clusion(MCAo)models and thromboembolic models are the most commonly used in simulating human ischemic stroke.The endovascular filament occlusion model is characterized by easy manipulation and accurately controllable reperfusion and is suitable for studying the pathogenesis of focal ischemic stroke and reperfusion in-jury.Although the reproducibility of the embolic model is poor,it is more conveni-ent for investigating thrombolysis.Rats are the most frequently used animal model for stroke.This review mainly outlines the stroke models of rats and discusses their strengths and shortcomings in detail.
文摘目的探究阿托伐他汀对高血糖诱导的小鼠脑缺血后出血转化(HT)的作用及机制。方法36只SPF级雄性C57BL/6小鼠随机分为假手术组、HT模型组和阿托伐他汀组,每组12只。比较各组小鼠神经功能评分、死亡率、HT发生率、HT分级评分,苏木精-伊红染色观察脑组织出血情况,免疫荧光染色评估血脑屏障通透性,Western blot检测缺血半暗带脑组织免疫球蛋白G(IgG)、闭锁连接蛋白1(ZO-1)、闭合蛋白(occludin)、紧密连接蛋白5(claudin5)、基质金属蛋白酶(MMP)2和MMP-9的蛋白表达。结果与假手术组比较,HT模型组神经功能评分、死亡率、HT发生率、HT评分、IgG荧光强度、IgG、MMP-2、MMP-9蛋白表达水平显著增高,ZO-1、occludin、claudin5蛋白表达水平明显降低(P<0.01)。与HT模型组比较,阿托伐他汀组神经功能评分、死亡率、HT发生率、HT评分、IgG荧光强度及IgG、MMP-2、MMP-9蛋白表达水平显著降低[(2.73±1.19)分vs(3.91±0.94)分,16.7%vs 41.6%,58.3%vs 91.6%,(1.00±1.04)分vs(2.58±1.13)分,(504.30±105.52)a.u vs(859.91±153.28)a.u,4.55±1.40 vs 12.06±3.73,1.87±0.41 vs 2.95±0.68,1.47±0.24 vs 2.12±0.23,P<0.05,P<0.01],ZO-1、occludin、claduin5蛋白表达显著升高(1.55±0.20 vs 0.53±0.10,0.92±0.11 vs 0.35±0.07、0.58±0.04 vs 0.30±0.05,P<0.01)。结论阿托伐他汀可通过抑制MMP-2、MMP-9激活,上调ZO-1、occludin、claudin5表达,降低血脑屏障通透性,从而抑制高血糖诱导的脑缺血后HT。
文摘目的系统评价急性缺血性卒中静脉溶栓后症状性颅内出血预测模型的特征,为静脉溶栓临床决策提供参考。方法检索中国知网、万方数据知识服务平台、维普资讯、PubMed、Embase、Web of Science和The Cochrane Library数据库,收集急性缺血性卒中静脉溶栓后症状性颅内出血预测模型相关研究信息,检索时限为建库至2022年12月18日。由2位研究员独立筛选文献、提取资料并评价偏倚风险后对纳入模型的基本特征和方法论进行系统评价。结果纳入20项研究,共30个预测模型。纳入模型ROC曲线的AUC值范围为0.42~0.94。24个(80%)预测模型的整体预测性能较好,模型对不同结局的定义和算法的区分度有明显差异。最常见的预测因子包括NIHSS评分、年龄、梗死的影像学征象或评分、血糖、收缩压和抗血小板药物。结论急性缺血性卒中静脉溶栓后症状性颅内出血预测模型呈现出建模算法多样化、模型性能更佳化、预测因素多元化等特点,但总体偏倚风险较高,未来研究还需要进一步校准模型。此外,应更加关注模型的更新与外部验证,提高其外推性及临床效用,从而发挥模型更大的临床价值。
