High NaCl predisposes Dahl rats to cerebral infarction after middle cerebral artery occlusion

High (8%) and low (0.3%) NaCl diets were administered for 3 weeks before testing inbred Dahl salt-sensitive (SS/Jr) or salt-resistant rats (SR/Jr) for altered susceptibility to cerebral infarction after occlusion of the middle cerebral artery. At occlusion time, mean systolic blood pressure (BP) was 201 +/- 7 mm Hg in SS/Jr fed a high NaCl diet. Two weeks later an atrophied infarct was present in the territory of the occluded artery of all (n = 10) hypertensive SS/Jr, and infarct size was correlated with BP at occlusion time (p less than 0.01). In normotensive control SS/Jr fed a low NaCl diet (n = 11), BP (118 +/- 3 mm Hg), frequency of infarction (18%), and infarct size were all significantly less (p less than 0.05) than in the hypertensive rats. In SR/Jr fed a high (n = 11) or low (n = 10) NaCl diet, BP was not statistically different (112 +/- 4 vs 116 +/- 4 mm Hg). Cerebral infarction frequency was significantly (p less than 0.05) greater in SR/Jr fed a high NaCl diet (73%) than in SR/Jr receiving a low NaCl diet (20%), but infarct size was not correlated with BP in SR/Jr (p greater than 0.05). Thus, elevated NaCl intake in SS/Jr and SR/Jr before middle cerebral artery occlusion predisposes to cerebral infarction, but differences in infarct size and its correlation with BP suggest the controlling factors are not identical in the two strains.     

Effects of blockade of cerebral lymphatic drainage on cerebral ischemia after middle cerebral artery occlusion in rats

This experiment aimed to investigate the effects of blockade of cerebral lymphatic drainage on cerebral ischemic damage. Seventy six Wistar rats were divided randomly into middle cerebral artery occlusion (MCAO) group and MCAO plus cerebral lymphatic blockade (MCAO+CLB) group for the experiment. The contents of water and electrolytes, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the ischemic brain tissue were detected at 24, 48 and 72 hours after the operation. The morphologic examination was also performed. In MCAO group, contents of water, sodium and calcium in the ischemic brain tissue increased significantly at any time after the operation. The SOD activity decreased while the MDA content increased markedly. The morphologic findings showed severe damage of ischemic brain tissue and neurons. In MCAO+CLB group, the above parameters were altered more obviously. The present observation suggests that blockade of cerebral lymphatic drainage may deteriorate ischemic brain damage after MCAO.     

改良大鼠大脑中动脉阻塞模型的建立

目的建立稳定、可靠的大鼠大脑中动脉阻塞(MCAO)改良模型。方法将60只SD雄性大鼠随机分为实验组和对照组,每组30只。实验组采用改良方法制作MCAO模型;对照组采用Longa传统方法制作模型。比较两组模型制作的成功率、脑梗死体积及模型稳定性。结果改良后的大鼠MCAO模型制作成功率和脑梗死体积分别为82·8%、(46±7)%,与对照组的89·3%、(48±7)%比较,差异无显著性(P>0·05)。实验组脑梗死体积变异系数为15·94%,对照组为16·21%,两组的模型稳定性相近。结论改良的大鼠MCAO模型是一种稳定性好、成功率高的脑缺血-再灌注模型。     

Effect of age in rats following middle cerebral artery occlusion

BACKGROUND: Despite the impressive increased understanding of the ischemic brain damage in general, the study of effects on different age groups, young versus old, using comparable ischemic insults is clearly lacking. OBJECTIVES: To investigate the mortality rate and neurological outcome among young and old rats, through a model of cerebral ischemia by middle cerebral artery occlusion (MCAO). METHODS: Twenty-three old (22-24 months of age) and 16 young (3-4 months of age) male rats underwent a MCAO procedure for 60 min. Surviving rats were randomly assigned to the 24-hour or 28-day resting group. The mortality rate and neurological outcome in different recovery time periods were determined for comparison between the young and old rats. RESULTS: The overall mortality rate in old rats (43.5%) was significantly higher than that of the young rats (6.3%) (p = 0.01). The infarct volume for the 24-hour post-MCAO was 181.86 +/- 11.87 mm(3) for the young rats, and 204.64 +/- 27.18 mm(3) for the old rats. For the 28-day post-MCAO, the value was 91.16 +/- 3.59 mm(3) for the young rats, and 103.38 +/- 26.43 mm(3) for the old rats. A significant reduction in infarct volume is noted in both young (p < 0.01) and old (p < 0.05) rats after 28 days of recovery compared to that after 24 h of recovery. There was no meaningful difference in infarct volume between the young and old rats measured at 24 h or 28 days after the ischemic procedure. The right volume was larger than the left volume at 24 h post-MCAO for both the young and the old rats, whereas the quotient approached unity for the young rats at 28 days post-MCAO. For the old rats, the quotient was negative at 28 days post-MCAO, representing the ipsilateral hemisphere was smaller than the contralateral hemisphere. CONCLUSION: The mortality risk to ischemic damage is greater for old rats. If an old rat survives the high-risk mortality in a short period after the MCAO procedure, the recovery would be of no difference to that of a young rat.     

交感神经活性对大脑中动脉闭塞大鼠外周免疫功能的影响

目的 探讨交感神经系统活性变化与脑梗死后外周细胞免疫功能抑制之间的关系.方法 成年雄性Sprague -Dawley大鼠制作大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型.采用双抗体夹心酶联免疫吸附法测定大鼠血清促炎细胞因子白细胞介素(interleukin,IL)-1...     

乙醛脱氢酶2对大脑中动脉阻塞大鼠的脑损伤保护作用

目的探讨乙醛脱氢酶2(ALDH2)对大脑中动脉栓塞(MCAO)大鼠的保护作用。方法选择SD大鼠200只,采用MCAO制作大鼠脑缺血模型,分为对照组、激动剂组(激动剂Adal1)和阻断剂组(阻断剂Cya)、LV-ALDH2组(ALDH2转基因慢病毒)和sh-ALDH2组(RNA干扰ALDH2),观察ALDH2活力和大鼠脑梗死面积及神经行为学评分。结果与对照组比较,激动剂组和LV-ALDH2组增加ALDH2的活力、减少脑梗死面积和神经行为学评分(P<0.05,P<0.01);阻断剂组和sh-ALDH2组降低ALDH2活力,增大脑梗死面积和神经行为学评分(P<0.05)。结论激活ALDH2能减轻MCAO大鼠的脑梗死面积和改善神经行为功能,对缺血性脑损伤有保护作用。     

阿托伐他汀对大脑中动脉栓塞大鼠尿激酶溶栓治疗的影响

目的研究阿托伐他汀联合尿激酶溶栓对大鼠大脑中动脉急性脑梗死的疗效。方法选择SD大鼠48只,采用血栓栓塞法制备大鼠大脑中动脉急性脑梗死模型,随机分为阿托伐他汀组、尿激酶组、联合治疗组和对照组,每组12只。缺血3h给予阿托伐他汀或生理盐水,缺血4h给予尿激酶或生理盐水治疗。治疗前和缺血24h行神经功能缺损评分,缺血24h取脑行2,3,5-氯化三苯基四氮唑染色检测脑梗死体积。结果与对照组比较,阿托伐他汀组缺血24h神经功能显著改善[(6.5±4.3)分vs(12.5±4.3)分],脑梗死体积明显降低[(13.8±7.5)%vs(30.5±23.4)%,P<0.05]。与阿托伐他汀组比较,尿激酶组和联合治疗组神经功能改善程度及脑梗死体积降低程度更显著(P<0.05)。与尿激酶组比较,联合治疗组神经功能改善、脑梗死体积减小,但差异无统计学意义(P>0.05)。结论阿托伐他汀对脑梗死组织有保护作用,阿托伐他汀与尿激酶联合治疗有进一步提高疗效的趋势。     

Melatonin suppresses cerebral edema caused by middle cerebral artery occlusion/reperfusion in rats assessed by magnetic resonance imaging

Melatonin, a pineal secretory product synthesized from tryptophan, has been found to be effective against neurotoxicity. The present study was aimed at demonstrating the effectiveness of melatonin in vivo in reducing ischemia-induced cerebral edema using magnetic resonance imaging (MRI). Rats were subjected to middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was administered twice (6.0 mg/kg, p.o.) just prior to 1 hr of MCA occlusion and 1 day after the surgery. T2-weighted multislice spin-echo images were acquired 1 day after the surgery. In the saline-treated control rats, increases in T2-weighted signals (water content) were clearly observed in the striatum and in the cerebral cortex. In the melatonin-treated group, total volume of edema was reduced by 51.6% compared with control group (P < 0.01). The protective effect of melatonin against edema was more clearly observed in the cerebral cortex (reduced by 59.8%, P < 0.01) than in the striatum (reduced by 34.2%, P < 0.05). Edema volume in a coronal slice was the greatest at the level of the bregma. Suppression of cerebral edema by melatonin was more effective posterior than anterior to the bregma. Melatonin appeared to reduce the volume of the edematous sites rather than to shift the signal intensity distribution. The present MRI study clearly demonstrates the effectiveness of melatonin against cerebral edema formation in ischemic animals in vivo, especially in the cerebral cortex. Melatonin may be highly useful in preventing cortical dysfunctions such as motor, sensory, memory, and psychological impairments associated with ischemic stroke.     

松龄血脉康预处理对脑缺血再灌注大鼠脑组织基质金属蛋白酶-9表达的影响

目的 探讨松龄血脉康预处理对脑缺血再灌注大鼠脑组织基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)表达的影响.方法 45只雄性SD大鼠,随机分为松龄血脉康(SL-xmk)预处理组、假手术组和生理盐水对照组.SL-xmk预处理组采用SL-xmk悬浮液(937.5 mg/kg)对大鼠...     

脑缺血预处理对脑缺血再灌注大鼠血脑屏障通透性和基质金属蛋白酶-9表达的影响

Objective To investigate the effects of ischemic preconditioning (IP) on blood-brain barrier permeability and matrix metalloproteinase-9 expression after cerebral ischemia reperfusion in rats.Methods A total of 154 Wistar rats were randomly divided into sham operation (n = 14),non-ischemic preconditioning (NIP,n = 70),and IP (n = 70) group.The latter two groups were redivided into 5 subgroups (n = 14 in each subgroup).A middle cerebral artery occlusion model was induced by intraluminal suture method.After 10 minutes IP,re-ischemia for 2 hours and reperfusion for 22 hours were performed at day 1,3,7,14,and 21,respectively.The infarct volume was detected using 2,3,5-triphenyltetrazolium chloride (TTC)staining.The BBB permeability were evaluated by measuring the content of the extravascular exudation of Evan's blue (EB).The degree of cerebral edema was evaluated using the wet-dry weight method.MMP-9 protein and mRNA expression were detected by immunohistochemical staining and in situ hybridization.Results Compared to the corresponding subgroups in the NIP group,the neurological deficit scores,infarct volume,EB content,and brain water content were decreased significantly,and MMP-9 protein and mRNA expression were down-regulated significantly in the day 1,3,and 7 subgroups in the IP group (P ＜ 0.05 or P ＜ 0.01 ).The infarct volume and MMP-9 mRNA expression of the day 1,3,7 subgroups in the IP group were more significantly reduced or down-regulated than those of the day 14 and21 subgroups in the IP group.The EB content,brain water content,and MMP-9 protein expression of the day 3 and 7 subgroups were more significantly lower than those in other subgroups.Among them,they were decreased most significantly in the day 3 subgroup (P ＜ 0.05).Conclusions The changes of IP-induced BBB permeability and the down-regulated MMP-9 expression may play important roles in cerebral ischemic tolerance.     

脑缺血预处理对脑缺血再灌注大鼠血脑屏障通透性和基质金属蛋白酶-9表达的影响

目的 探讨脑缺血预处理(ischemic preconditioning,IP)对脑缺血再灌注大鼠血脑屏障通透性和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)表达的影响.方法 154只Wistar大鼠随机分为假手术组(14只)、非缺血预处理(non-ischemic preconditioning,NIP)组(70只)和IP组(70只),后两组再随机分为5个亚组,每组14只.线栓法建立大脑中动脉闭塞模型,缺血预处理10 min,分别在IP后1、3、7、14和21 d进行再次缺血2 h再灌注22 h.采用2,3,5-氯化三苯基四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色测定脑梗死体积,通过测定渗出血管外的伊文思蓝(Evans blue,EB)含量评价血脑屏障通透性,采用于湿重法评价脑水肿程度,免疫组化染色和原位杂交法检测MMP-9蛋白和mRNA表达.结果 与NIP组相应亚组比较,IP组缺血预处理1、3和7 d亚组神经功能缺损评分显著降低,脑梗死体积显著缩小,EB含量和脑水含量显著降低,MMP-9蛋白和mRNA表达均显著下调(P＜0.05或P＜0.01).IP组1、3和7 d亚组梗死体积和MMP-9 mRNA表达较IP组14 d和21 d亚组显著缩小或下调,3 d和7 d亚组EB含量、脑水含量和MMP-9蛋白表达较其他亚组显著降低,其中以3 d亚组降低最显著(P＜0.05).结论 缺血预处理诱导的血脑屏障通透性改变和MMP-9表达下调在脑缺血耐受中发挥着重要作用.     

Treadmill training effects in different age groups following middle cerebral artery occlusion in rats

BACKGROUND: Despite the increased understanding of treadmill training on stroke patients, its effects on different age groups are not clearly known. The present study presents such effects through a model of cerebral ischemia on young and old groups of rats. OBJECTIVES: To investigate the effect of treadmill training on young and old rats after cerebral ischemia caused by middle cerebral artery occlusion (MCAO). METHODS: Forty old (22-24 months of age) and 32 young (3-4 months of age) rats underwent the MCAO procedure for 60 min. Rats that survived the procedure were randomly assigned to a 1- or a 2-week treadmill training group, or a time-matched control group (n=6-8 for each group). The infarct volume was compared between the treadmill training and the control groups for both the young and old rats at 1 or 2 weeks. RESULTS: After treadmill training for 1 week, the mean infarct volume was 7.26+/-0.49 and 9.51+/-0.84% for the young and old rats, respectively. The 1-week treadmill training effect was significant in the young rats (p=0.0207) but not in the old rats (p=0.0840). The mean infarct volume was 6.84+/-0.51 and 7.63+/-0.52% for the young and old rats, respectively, after the 2-week treadmill training. Both the young and old rat groups demonstrated a significant reduction in the infarct volume compared with that of the control group (p=0.021 for the young group and p=0.039 for the old group) after 2 weeks of treadmill training. CONCLUSION: The present findings clearly demonstrate the different training effects of locomotor activity in reducing ischemic infarction in young and old rats. The delayed reduction in ischemic infarction in old rats was notable and may be attributable to the slow response of angiogenic and neurogenic mechanisms in the old rats.     

大鼠大脑中动脉阻塞模型建立时的麻醉方式选择

目的探讨腹腔麻醉与吸入麻醉方式对建立大鼠大脑中动脉阻塞(MCAO)脑缺血再灌注模型的影响。方法将64只大鼠随机分为两组,分别应用水合氯醛腹腔注射麻醉法和气管插管2%七氟烷混合30%氧气吸入麻醉法进行麻醉,Longa法建立MCAO模型。观察两组大鼠的麻醉诱导、持续及苏醒时间的差异,对比分析血气分析、血糖、肛温、脑温、神经功能缺失评分、48h存活情况以及梗死体积的差异。结果水合氯醛腹腔注射麻醉对呼吸有明显抑制,血气分析显示有严重的呼吸性酸中毒[pH7.29±0.03,PCO2(56.8±4.2)mmHg,PO2(119.1±15.6)mmHg],吸入麻醉组辅助呼吸,血气分析正常[pH7.48±0.06,PCO2(36.2±0.3)mmHg,PO2(219.1±27.4)mmHg]。两组大鼠的pH值、PCO2、PO2相比差异均有显著性(P<0.01)。腹腔麻醉能显著降低脑温和肛温[梗死区皮质温度(33.3±0.8)℃、纹状体温度(33.6±0.3)℃、肛温(34.7±0.5)℃],吸入麻醉对脑温和肛温影响较小[梗死区皮质温度(35.1±0.3)℃、纹状体温度(36.2±0.3)℃、肛温(35.1±0.3)℃],两组间脑温比较差异有显著性(P<0.01),而肛温间差异无显著性(P>0.05)。大鼠48h存活只数及脑梗死体积在腹腔麻醉组与吸入麻醉组之间差异均无显著性(P>0.05)。结论建立大鼠MCAO模型时,应用吸入麻醉明显优于腹腔麻醉,其对呼吸、血糖、脑温等指标影响较小,有利于建立稳定的大鼠MCAO模型。     

Endovascular middle cerebral artery occlusion in rats as a model for studying vascular dementia

Vascular dementia (VaD), incorporating cognitive dysfunction with vascular disease, ranks as the second leading cause of dementia in the United States, yet no effective treatment is currently available. The challenge of defining the pathological substrates of VaD is complicated by the heterogeneous nature of cerebrovascular disease and coexistence of other pathologies, including Alzheimer’s disease (AD) types of lesion. The use of rodent models of ischemic stroke may help to elucidate the type of lesions that are responsible for cognitive impairment in humans. Endovascular middle cerebral artery (MCA) occlusion in rats is considered to be a convenient and reliable model of human cerebral ischemia. Both sensorimotor and cognitive dysfunction can be induced in the rat endovascular MCA occlusion model, yet sensorimotor deficits induced by endovascular MCA occlusion may improve with time, whereas data presented in this review suggest that in rats this model can result in a progressive course of cognitive impairment that is consistent with the clinical progression of VaD. Thus far, experimental studies using this model have demonstrated a direct interaction of cerebral ischemic damage and AD-type neuropathologies in the primary ischemic area. Further, coincident to the progressive decline of cognitive function, a delayed neurodegeneration in a remote area, distal to the primary ischemic area, the hippocampus, has been demonstrated in a rat endovascular MCA occlusion model. We argue that this model could be employed to study VaD and provide insight into some of the pathophysiological mechanisms of VaD.     

变构促红细胞生成素对中年雌性脑缺血小鼠白质损伤的作用研究

目的 研究变构促红细胞生成素(MEPO)对成年雌性脑缺血小鼠白质的保护作用.方法 将30只成年雌性C57BL/6J小鼠按随机数字表法完全随机分为3组:假手术组(Sham组),脑缺血模型组(Vehicle组)及脑缺血MEPO治疗组(MEPO组),每组10只.采用大脑中动脉远端血管永久性闭塞的方式制备小鼠脑缺血模型.MEP...     

尿激酶溶栓对大脑中动脉血栓栓塞模型大鼠MMP-9、血脑屏障通透性和脑出血的影响

目的 观察栓塞性脑缺血后及应用尿激酶(urokinase,UK)溶栓后基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的表达及对脑出血量和血脑屏障通透性的影响,探讨MMP-9与血脑屏障通透性和溶栓后脑出血之间的关系.方法 通过颈动脉内注射自体血制作大鼠血栓栓塞性大脑中动脉闭摩模型,缺血6h后静脉应用UK,24 h后分别采用免疫组化法检测脑组织MMP-9表达、伊文思蓝渗出法检测血脑屏障通透性、TTC染色法检测脑梗死体积、分光光度法检测脑出血量.结果 脑缺血组MMP-9表达显著高于假手术组(P＜0.01),UK溶栓组显著高于脑缺血组(P＜0.01).脑缺血组伊文思蓝含量为(5774.00±1659.70)ng/g,显著高于假手术组的(643.33±151.34)ng/g(P＜0.01),UK溶柃组为(6283.83±1099.28)ng/g,有高于脑缺血组的趋势.UK溶柃组和脑缺血组脑出血量分别为(3.16±8.84)μl(中位数±四分位数)和(0.00±1.48)μl,脑出血发生率分别为25.00%和4.17%.结论 UK溶栓可能上调 MMP-9表达,MMP-9表达与BBB通透性增加与溶栓后脑出血有关.     

脑梗死后脑红蛋白的表达及其保护机制

目的探讨脑梗死后缺血半暗带脑组织中脑红蛋白（NGB）表达与caspase-3、谷氨酸表达的关系及NGB在脑缺血中的表达规律和保护作用的机制。方法制作大鼠局灶性脑缺血模型（MCAO）,随机分为假手术对照组、脑缺血组和单克隆NGB抗体干预组、干预对照组、正常干预对照组,分别在不同时间点断头取脑,制作标本,作脑红蛋白、caspase-3和谷氨酸免疫组化染色。结果（1）与假手术对照组比较,缺血5min亚组可见NGB阳性细胞数开始上升,0.5h达到高峰（P〈0.01）,随后下降,至6h接近假手术组。缺血各组（除24h、72h外）之间两两比较,差异均有统计学意义（P〈0.01）;（2）与假手术对照组比较,缺血0.5h亚组大脑皮质与豆状核区细胞caspase-3阳性表达增多,6～24h达到高峰（P〈0.01）,72h时仍高于假手术对照组,缺血各亚组之间两两比较,差异均有统计学意义（P〈0.01）;（3）与假手术对照组比较,缺血各亚组大脑皮质与豆状核区细胞谷氨酸阳性表达缺血0.5h就已增多,且随时间的变化呈逐步增高的趋势,24～72h达到高峰（P〈0.01）,缺血各亚组之间两两比较,差异均有统计学意义（P〈0.01）;（4）NGB表达与caspase-3、谷氨酸表达均呈负相关关系（分别为r=-0.953,P〈0.01;r=-0.973,P〈0.01）;（5）干预对照组caspase-3、谷氨酸表达均上调（P〈0.01）。结论脑缺血后NGB在缺血周围半暗带区早期表达升高,随后下降,于6h后降至正常,具有调节caspase-3、谷氨酸表达的作用,这是NGB脑保护作用的可能机制。     

老龄大鼠线栓和自体血栓性大脑中动脉闭塞模型的比较研究

目的　探索一种适合于老龄大鼠脑梗死研究的大脑中动脉闭塞 (MCAO)模型。方法　用神经功能缺损评分、墨汁或 TTC染色、病理学观察以及脑组织含水量测定等方法比较研究老龄大鼠线栓与改良自体血栓 MCAO模型的稳定性。结果　血栓组与线栓组成功率分别为 95.83%和 1 5% ,前者神经功能缺损较后者重 (评分为 8.59± 3.52与 1 4 .0 6± 4.0 4 ,P=0 .0 0 1 ) ,前者梗死体积亦高于后者 (2 60 .67± 1 4 .65mm3与 1 51 .0 0±98.1 4 mm3 ,P<0 .0 5) ;脑组织含水量血栓组明显高于线栓组 (P=0 .0 0 1 )。后者蛛网膜下腔出血的发生率为 2 %。结论　自体血栓性 MCAO模型成功率高、梗死范围恒定、可重复性好 ,较线栓更适合于老龄大鼠局灶性脑缺血的研究。