Prolonged but delayed postischemic hypothermia: a long-term outcome study in the rat middle cerebral artery occlusion model.

Delayed but prolonged hypothermia persistently decreases cell death and functional deficits after global cerebral ischemia in rodents. Postischemic hypothermia also reduces infarction after middle cerebral artery occlusion (MCAO) in rat. Because initial neuroprotection is sometimes transient and may not subserve functional recovery, especially on demanding tasks, the authors examined whether postischemic cooling would persistently reduce infarction and forelimb reaching deficits after MCAO. Male spontaneously hypertensive rats were trained to retrieve food pellets in a staircase test that measures independent forelimb reaching ability. Later, rats underwent 90 minutes of normothermic MCAO, through a microclip, or sham operation. In some rats, prolonged cooling (33 degrees C for 24 hours and then 35 degrees C for 24 hours) began 2.5 hours after the onset of ischemia (60 minutes after the start of reperfusion; n = 17 with subsequently 1 death) or sham procedures (n = 4), whereas untreated sham (n = 4) and ischemic (n = 16 with subsequently 1 death) rats maintained normothermia. An indwelling abdominal probe continually measured core temperature, and an automated fan and water spray system was used to produce hypothermia. One month later rats were reassessed in the staircase test over five days and then killed. The contralateral limb impairment in food pellet retrieval was completely prevented by hypothermia (P = 0.0001). Hypothermia reduced an infarct volume of 67.5 mm3 after untreated ischemia to 35.8 mm3 (P < 0.0001). These findings of persistent benefit encourage the clinical assessment of hypothermia.     

依托咪酯预处理对大鼠局灶性脑缺血-再灌注损伤的保护作用

目的 探讨依托咪酯预处理对脑缺血-再灌注损伤的保护作用。方法 18只雄性SD大鼠,随机均分为3组,即脑缺血-再灌注组、依托咪酯预处理组、脂微球对照组。采用颈内动脉线栓栓塞致大脑中动脉阻塞模型,监测肛温及血糖,并于再灌注24h后断头处死动物,取大脑切片行2,3,5-氯化三苯基四氮唑染色,测量并计算脑梗死容积百分比。结果 依托咪酯预处理组脑梗死百分比明显低于脂微球对照组（P＜0.01）,低于缺血-再灌注组（P＜0.05）。但缺血-再灌注组与脂微球对照组相比差异无统计学意义。结论 依托咪酯预处理后可明显减小大鼠局灶性脑缺血-再灌注损伤后的脑梗死面积。     

The angiotensin II type 1-receptor blocker candesartan increases cerebral blood flow, reduces infarct size, and improves neurologic outcome after transient cerebral ischemia in rats.

The goal of the present study was to test the impact of administration time of the angiotensin II type 1-receptor blocker candesartan on cerebral blood flow (CBF), infarct size, and neuroscore in transient cerebral ischemia. Therefore, 1-hour middle cerebral artery occlusion (MCAO) was followed by reperfusion. Rats received 0.5-mg/kg candesartan intravenously 2 hours before MCAO (pretreatment), 24 hours after MCAO, every 24 hours after MCAO, or 2 hours before and every 24 hours after MCAO. Infarct size (mm3) and a neuroscore at day 7 were compared with controls. CBF was quantified by radiolabeled microspheres and laser-Doppler flowmetry. Compared with controls (95 +/- 8), infarct size in candesartan-treated groups was smaller (59 +/- 5, 68 +/- 10, 28 +/- 3, and 15 +/- 3, respectively; P<0.05). Although there was no difference in neuroscore between pretreatment and controls (1.55 +/- 0.18, 1.80 +/- 0.13), other treatment regimens resulted in improved neuroscores (1.33 +/- 0.16, 1.11 +/- 0.11, 0.73 +/- 0.15; P<0.05). CBF in pretreated animals at 0.5 hours after MCAO was significantly higher than in controls (0.58 +/- 0.09 mL x g(-1) x min(-1) and 44% +/- 7% of baseline compared with 0.49 +/- 0.06 mL x g(-1) x min(-1) and 37% +/- 6%, microspheres and laser-Doppler flowmetry; P<0.05). Thus, candesartan reduces infarct size even if administered only during reperfusion. Apart from pretreatment, other treatment regimens result in significantly improved neuroscores. In the acute phase of cerebral ischemia, candesartan increases CBF.     

局灶性缺血预处理对脑梗死大鼠神经生长因子表达的影响

目的:研究局灶性缺血预处理对脑梗死大鼠神经生长因子(nerve growthfactor,NGF)表达的影响,探讨缺 血预处理诱导脑缺血耐受机制。方法:SD大鼠随机分为3组。预缺血组和假手术组在大脑中动脉缺血(MCAO)前3天 分别接受10min的预缺血或假手术,MCAO 2h后再灌注22h处死;对照组两次均为假手术,比较各组神经功能评分、梗 死体积及NGF的表达。结果:预缺血组神经功能评分、梗死体积较假手术组减少(P<0．05),NGF表达明显高于其余两 组(P<0．01)。结论:局灶性缺血预处理可诱导脑缺血耐受的产生,其作用机制可能与NGF的表达改变有关。     

厄贝沙坦对大鼠局灶性脑缺血再灌注后炎症反应的影响

目的观察厄贝沙坦对大鼠局灶性脑缺血再灌注后脑内及外周炎症反应的影响。方法采用改良Longa方法制备大鼠大脑中动脉阻塞(middle cerebralartery occlusion,MCAO)模型,于缺血90min再灌注后24h和72h进行梗死体积的测量,采用免疫组化和ELISA方法测量脑内和外周血的粘附分子。结果厄贝沙坦可以显著减少局灶性脑缺血再灌注后24h和72h的梗死体积(均P<0.01),改善神经功能(均P<0.01);降低脑内ICAM-1、VCAM-1的表达及其外周血浆中可溶性的形式sICAM-1、sVCAM-1蛋白的水平(均P<0.05)。结论厄贝沙坦可以降低粘附分子的表达,减少梗死体积,改善神经功能,对脑缺血再灌注起保护作用。     

Deficiency of PAR-2 gene increases acute focal ischemic brain injury.

The expression profile of the protease-activated receptor-2 (PAR-2) and effects of PAR-2 gene knockout (PAR-2 KO) on the infarct size were investigated after 60 minutes of transient middle cerebral artery occlusion (tMCAO) in mice in relation to phosphorylated extracellular signal-regulated kinase (p-ERK) and astrocyte activation. PAR-2 was normally distributed mainly in neurons of the central nervous system (CNS), and strongly upregulated at 8-24 hours after tMCAO. Deficiency of PAR-2 gene significantly increased the infarct volume and the number of TUNEL-positive cells at 24 hours of reperfusion. The strong neuronal expression of p-ERK was induced at 5 minutes as a peak after reperfusion in wild-type mice, but the signal change was significantly reduced in PAR-2 KO mice. Astroglial activation was also greatly inhibited at 24 hours after tMCAO in PAR-2 KO mice. These results show that the deficiency of PAR-2 gene increases the acute ischemic cerebral injury associating with suppression of neuronal ERK activation and reactive astroglial activation.     

Neuroprotective effects of the CRF1 antagonist R121920 after permanent focal ischemia in the rat.

The neuroprotective effects of a systemically active, highly selective, corticotropin-releasing factor-1 (CRF1) receptor antagonist, R121920 ((7-(dipropylamino)-2,5-dimethyl-3- [2-(dimethylamino)-5-pyridyl] pyrazolo [1,5-a] pyrimidine), was assessed in two rat models of permanent focal cerebral ischemia, where the middle cerebral artery (MCA) was occluded either through the subtemporal approach or using the intraluminal suture technique. R121920 rapidly crossed the blood-brain barrier after intravenous (IV) bolus administration (10 mg/kg), with peak brain concentrations at 5 minutes (2.26 +/- 0.40 microg/mL), which were approximately 2-fold greater than those in plasma (0.98 +/- 0.24 microg/mL). Treatment with R121920 (10 mg/kg IV followed by 5 mg/kg subcutaneously at hourly intervals for 4 hours) significantly (P < 0.001) reduced total (by 40%) and cortical (by 37%) infarct volume at 24 hours after subtemporal MCA occlusion (MCAO). In the intraluminal suture MCAO model, IV administration of R121920 (10 mg/kg) at the time of ischemia onset (and at multiple times thereafter) reduced both hemispheric infarct volume (by 34%, P < 0.001) and brain swelling (by 50%, P < 0.001) when assessed at 24 hours. In this model of focal ischemia, significant reduction (P < 0.05) in both outcome measures was obtained when R121920 administration was delayed up to 1 hour after MCAO. These results further define the antiischemic properties of selective CRF 1 antagonists in two experimental models of permanent focal cerebral ischemia.     

microRNA-455-5p alleviates neuroinflammation in cerebral ischemia/reperfusion injury

Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion.Downregulation of microRNA(miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia.However,the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated.In this study,mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion.Agomir-455-5p,antagomir-455-5p,and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion(MCAO).The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood.Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue,reduced the cerebral infarct volume,and improved neurological function.Furthermore,primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion.miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels,inhibited microglia activation,and reduced the production of the inflammatory factors tumor necrosis factor-αand interleukin-1β.These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.     

Thrombopoietin protects the brain and improves sensorimotor functions: reduction of stroke-induced MMP-9 upregulation and blood–brain barrier injury

This study was conducted to determine the protective efficacy and mechanisms of thrombopoietin (TPO) intervention in experimental focal stroke. Male rats underwent 2 hours of left middle cerebral artery occlusion (MCAO) followed by 22 hours of reperfusion. Vehicle or TPO (0.03 to 1.00 μg/kg) was administered intravenously immediately after reperfusion. Brain infarct and swelling, neurologic deficits, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), TPO and c-Mpl (TPO receptor) mRNA, MMP-9 enzyme activity and protein expression, and the integrity of the blood–brain barrier (BBB) were subsequently measured. MCAO reperfusion produced a large infarct and swelling after stroke. Thrombopoietin significantly reduced these in a dose-dependent manner. The most effective TPO dose, 0.1 μg/kg, when administrated immediately or 2 hours after reperfusion, significantly reduced infarct and swelling and ameliorated neurologic deficits after stroke. Stroke-induced increases in cortical MMP-9 mRNA, enzyme activity and protein expression, TIMP-1 mRNA, and Evans blue extravasation were reduced by TPO intervention. Thrombopoietin did not alter cortical TPO or c-Mpl mRNA expression, blood pressure, heart rate, blood hematocrit, or platelets. This is the first demonstration of TPO''s efficacy in reducing ischemic brain injury and improving functional outcome, partly by inhibiting the stroke-induced increase in MMP-9 and the early, negative effects on the BBB.     

Comet assay as a novel approach for studying DNA damage in focal cerebral ischemia: differential effects of NMDA receptor antagonists and poly(ADP-ribose) polymerase inhibitors.

The single-cell gel electrophoresis (comet assay) was used to evaluate the possibility of detecting single-strand breaks of brain DNA in the early phase of ischemia. Four hours after occlusion of the middle cerebral artery (MCAO) in rats, the percentage of DNA migrating into the comet tail (indicating the presence of breaks) increased from 11.4 +/- 4.70 to 34.7 +/- 9.2 (means +/- SD) in the caudate and from 9.9 +/- 4.3 to 42.8 +/- 14.1 in the cortex. Interestingly, a subpopulation of cells exhibiting higher resistance to the ischemic insult was present in the caudate putamen, but not in the cortex. Administration of MK801, an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, (1 mg/kg subcutaneously, 10 minutes before MCAO), reduced the ischemia-induced DNA breaks and the infarct volume, suggesting that excessive stimulation of NMDA receptors contributes to the formation of both DNA damage and infarct volume. In contrast, DPQ, an inhibitor of poly(ADP-ribose) polymerase (PARP) (10 mg/kg intraperitoneally, 2 hours before and 1 hour after MCAO), reduced the infarct volume but not DNA damage, suggesting that the neuroprotective actions of PARP inhibitors occur at a later step of the processes leading to postischemic neuronal death.     

Cannabinoid CB(2) receptor activation decreases cerebral infarction in a mouse focal ischemia/reperfusion model.

Cannabinoid CB(2) Receptor (CB(2)) activation has been shown to have immunomodulatory properties without psychotropic effects. The hypothesis of this study is that selective CB(2) agonist treatment can attenuate cerebral ischemia/reperfusion injury. Selective CB(2) agonists (O-3853, O-1966) were administered intravenously 1 h before transient middle cerebral artery occlusion (MCAO) or 10 mins after reperfusion in male mice. Leukocyte/endothelial interactions were evaluated before MCAO, 1 h after MCAO, and 24 h after MCAO via a closed cranial window. Cerebral infarct volume and motor function were determined 24 h after MCAO. Administration of the selective CB(2) agonists significantly decreased cerebral infarction (30%) and improved motor function (P<0.05) after 1 h MCAO followed by 23 h reperfusion in mice. Transient ischemia in untreated animals was associated with a significant increase in leukocyte rolling and adhesion on both venules and arterioles (P<0.05), whereas the enhanced rolling and adhesion were attenuated by both selective CB(2) agonists administered either at 1 h before or after MCAO (P<0.05). CB(2) activation is associated with a reduction in white blood cell rolling and adhesion along cerebral vascular endothelial cells, a reduction in infarct size, and improved motor function after transient focal ischemia.     

胰岛素对局灶性脑缺血再灌注损伤的作用

目的　观察胰岛素对脑缺血再灌注损伤的治疗作用。方法　制备易卒中型肾血管性高血压大鼠（ Ｒ Ｈ Ｒ Ｓ Ｐ） ,用线栓法复制大脑中动脉阻塞（ Ｍ Ｃ Ａ Ｏ） ,造成缺血６ ｈ 再灌注１８ ｈ ,术后立即及６ 小时后即时使用胰岛素,测定神经功能障碍评分及脑梗死体积的变化。结果　胰岛素可使神经功能障碍评分显著减低,梗死灶体积及其占全大脑体积比值,两半球体积差值显著减小。结论　胰岛素能减轻脑缺血再灌注损伤,早期用药效果更好。     

局灶预缺血诱导脑缺血耐受的动物模型

目的　建立一种简便可靠的 SD大鼠局灶性脑缺血预处理模型。方法　将大鼠随机分为 3组 ,分别给予 10 m in大脑中动脉缺血 ( MCAO)预处理 ( PC) ;10 min PC后 2 h MCAO( PC MCAO)及假手术 ( SS)后 2 hMCAO( SS MCAO) ,再灌注 2 2 h后处死 ,观察各组神经功能缺损、梗死体积及脑含水量变化。结果　 PC MCAO组神经功能评分、梗死体积及含水量均明显低于 SS MCAO组 ,PC组无神经功能缺损及梗死灶形成。结论　 2次线栓法建立的大鼠局灶脑缺血预处理模型 ,能有效减轻 MCAO所致的神经损伤 ,操作简便 ,稳定性好 ,是一种研究局灶脑缺血耐受的有用工具。     

缺氧诱导因子-1α及促红细胞生成素在脑缺血耐受大鼠中的表达

目的 探讨缺氧诱导因子-1α（HIF-lα）及其靶基因促红细胞生成素（EPO）在脑缺血预处理诱导的大鼠脑缺血耐受机制中的作用。方法 将84只Wistar大鼠随机分成假手术对照组（SS+SS,4只）、假手术＋再缺血组（SS+MCAO,40只）、预缺血＋再缺血组（IP+MCAO,40只）,后两组再随机分成5个亚组。线栓法阻塞大脑中动脉建立局灶性缺血预处理模型（预缺血10 min）,分别在预缺血后1 d、3 d、7 d、14 d、21 d进行再次缺血2 h再灌注22 h,然后取脑组织进行脑梗死体积测量和病理观察,免疫组化方法检测HIF-lα与EPO蛋白的表达。结果 ⑴IP+MCAO组中1 d、3 d、7 d亚组的梗死体积与SS+MCAO各对应亚组相比明显减小;⑵IP+MCAO组1 d、3 d、7 d亚组中HIF-lα蛋白表达与SS+MCAO各对应亚组相比明显增高;IP+MCAO组3 d、7 d亚组中EPO蛋白表达与SS+MCAO各对应亚组相比明显增高。结论 缺血预处理诱导了脑缺血耐受,预缺血诱导的内源性HIF-lα及EPO蛋白表达增加参与脑缺血耐受形成的机制。     

Exendin-4对MCAO再灌注导致的脑缺血/再灌注损伤具有神经保护作用

目的 探讨GLP-1受体激动剂Exendin-4腹腔给药对大脑中动脉闭塞(MCAO)再灌注所致大鼠脑缺血/再灌注损伤的神经保护作用。方法 SD大鼠术前1 h腹腔注射Exendin-4,MCAO再灌注24 h后进行神经功能缺损评分,TTC染色计算脑梗死体积,免疫荧光观察神经元和小胶质细胞生存数量及检测凋亡通路相关蛋白的相对表达水平。结果 Exendin-4能够保护由于MCAO再灌注后所致的脑缺血再灌注损伤,减少了脑梗死体积,降低皮层凋亡蛋白的相对表达水平,抑制神经元凋亡。结论 Exendin-4可以对MCAO再灌注所致脑缺血/再灌注损伤具有神经保护作用,该作用是通过抑制凋亡蛋白的产生,从而抑制细胞凋亡。     

Secondary decline in apparent diffusion coefficient and neurological outcomes after a short period of focal brain ischemia in rats

This study was designed to characterize the initial and secondary changes of the apparent diffusion coefficient (ADC) of water with high temporal resolution measurements of ADC values and to correlate ADC changes with functional outcomes. Fourteen rats underwent 30 minutes of temporary middle cerebral artery occlusion (MCAO). Diffusion-, perfusion-, and T2-weighted imaging was performed during MCAO and every 30 minutes for a total of 12 hours after reperfusion (n = 6). Neurological outcomes were evaluated during MCAO, every 30 minutes for a total of 6 hours and at 24 hours after reperfusion (n = 8). The decreased cerebral blood flow during MCAO returned to normal after reperfusion and remained unchanged thereafter. The decreased ADC values during occlusion completely recovered at 1 hour after reperfusion. The renormalized ADC values started to decrease secondarily at 2.5 hours, accompanied by a delayed increase in T2 values. The ADC-defined secondary lesion grew over time and was 52% of the ADC-defined initial lesion at 12 hours. Histological evaluation demonstrated neuronal damage in the regions of secondary ADC decline. Complete resolution of neurological deficits was seen in 1 rat at 1 hour and in 6 rats between 2.5 and 6 hours after reperfusion; no secondary neurological deficits were observed at 24 hours. These data suggest that (1) a secondary ADC reduction occurs as early as 2.5 hours after reperfusion, evolves in a slow fashion, and is associated with neuronal injury; and (2) renormalization and secondary decline in ADC are not associated with neurological recovery and worsening, respectively.     

Effect of nicorandil on infarct volume and marker enzyme activity in mitochondria of rats with cerebral ischemia/ reperfusion injury

BACKGROUND: Recent studies have suggested that mitochondrial ATP-sensitive K channel openers could reduce myocardium infarct size, and protect the function of the mitochondria.OBJECTIVE: To investigate the changes of cerebral infarction volume and the activity of marker enzymes in brain mitochondria of rats given the ATP-sensitive K channel opener, nicorandil, before focal cerebral ischemia/reperfusion (I/R).DESIGN, TIME AND SETTING: Randomized, controlled animal experiment, completed at the Brain Scientific Research Center of the Affiliated Hospital of Qingdao University from July to November 2007.MATERIALS: Sixty healthy male Wistar rats weighing 280-300g. Nicorandil, 5-hydroxydecanoate (5-HD) and cytochrome C were purchased from Sigma in the USA. Standard malondialdehyde (MDA) and protein were purchased from Nanjing Jiancheng Biotechnology Institute.METHODS: Sixty rats were randomly divided into a sham operation group, a middle cerebral artery occlusion (MCAO) group, a nicorandil group and a nicorandil 5-HD group. MCAO for 2 hours was performed in the MCAO group, nicorandil group and nicorandil 5-HD group. A total of 5mL saline were given to the MCAO group before MCAO. The nicorandil group was injected with the ATP-sensitive K channel opener nicorandil 10mg/kg intraperitoneally 30 minutes before MCAO. The nicorandil 5-HD group was injected with 5-HD 10mg/kg intravenously 15 minutes before the same treatment as the nicorandil group.MAIN OUTCOME MEASURES: Infarct volume by total brain slice calculation, activities of succinate dehydrogenase (SDH) and cytochrome oxidase (CO), and content of MDA were observed at 22 hours of reperfusion after 2 hours MCAO.RESULTS: Sixty rats were included in the final analysis, without any loss. (1) Infarct volume: compared with the MCAO group and nicorandil 5-HD group, the percentage of infarct volume was significantly decreased in the nicorandil group (P<0.01). (2) The content of MDA, expression of SDH and CO in brain: the expressions of SDH and CO in the sham operation group were significantly lower than those in the MCAO, nicorandil and nicorandil 5-HD groups (P<0.01). The expressions of SDH and CO in the nicorandil group were significantly higher than those in the MCAO and nicorandil 5-HD groups (P<0.05). The content of MDA in the brain of the nicorandil group was significantly lower than those in the MCAO and nicorandil 5-HD groups (P<0.01).CONCLUSION: Nicorandil can significantly reduce the infarct volume in a rat MCAO model, increase the activity of the mitochondria and protect against cerebral I/R injury.     

Effects of combined estrogen and progesterone on brain infarction in reproductively senescent female rats.

Recent data from the Women's Health Initiative have highlighted many fundamental issues about the utility and safety of long-term estrogen use in women. Current hormone replacement therapy for postmenopausal women incorporates progestin with estrogen, but it is uncertain if combined therapy provides major cerebrovascular risks or benefits to these women. No experimental animal stroke studies have examined combined hormone administration. The authors tested the hypothesis that combined hormone treatment reduces ischemic injury in middle-aged female rat brain. Reproductively senescent female rats underwent 2-hour middle cerebral artery occlusion (MCAO) followed by 22 hours reperfusion. Estrogen implants were placed subcutaneously at least 7 days before MCAO, and progesterone intraperitoneal injections were given 30 minutes before MCAO, at initiation, and at 6 hours of reperfusion. Rats received no hormone, a 25-microg estrogen implant, a 25-microg estrogen implant plus 5 mg/kg intraperitoneal progesterone, or 5 mg/kg intraperitoneal progesterone. Cortical, caudoputamen, and total infarct volumes were assessed by 2,3,5-triphenyltetrazolium chloride staining and digital image analysis at 22 hours reperfusion. Cortical and total infarct volumes, except in the acute progesterone-treated group, were significantly attenuated in all estrogen-alone and combined hormone-treated groups. There were no significant differences in caudoputamen infarct volumes in all hormone-treated groups as compared with untreated rats. These data have potential clinical implications relative to stroke for postmenopausal women taking combined hormone replacement therapy.     

神经调节素1β通过激活Sirt1信号通路抑制自噬改善大鼠脑缺血再灌注损伤研究

目的 探讨神经调节素1β(neuregulin1β,NRG1β)是否通过抑制自噬减轻大鼠大脑中动脉缺血再灌注（middle cerebral artery occlusion reperfusion,MCAO/R）损伤,以及对沉默信息调节因子1(silent information regulator protein 1,Sirt1)信号通路的影响。方法 将210只健康雄性SD大鼠随机分为假手术组（Sham组）、模型组（MCAO/R组）、治疗组（NRG1β组）、激动剂组（SRT501组）、激动剂+治疗组（SRT501+NRG1β组）、抑制剂组（EX527组）和抑制剂+治疗组（EX527+NRG1β组）,每组30只。采用改良线栓法建立MCAO/R模型,线栓由颈外动脉插入颈内动脉18～22 mm,堵塞左侧大脑中动脉起始部。缺血2 h后,缓慢拔出线栓,恢复脑血流22 h。EX527(5 mg/kg)、SRT501(100 mg/kg)于术前30 min腹腔注射,NRG1β(2μg/kg)于拔出线栓后由微量注射器注入颈内动脉。脑缺血2 h、再灌注22 h后采用改良神经损伤严重程度评分（modi...     

阿托伐他汀对大鼠脑缺血再灌注后梗死灶周围中性粒细胞浸润和核转录因子-κB表达水平的影响

目的 观察阿托伐他汀对大鼠脑缺血再灌注后梗死灶周围中性粒细胞浸润以及核转录因子-κB表达水平的影响.方法 采用常规尼龙线栓法制备SD大鼠脑缺血再灌注模型,并将大鼠随机分为假手术组、大脑中动脉阻断再灌注(Middle cerebral artery occlusion/reperfusion,MCAO/R)(对照)组和M...