电刺激小脑顶核对大鼠脑缺血/再灌注后氧化性DNA损伤的保护作用

目的预电刺激小脑顶核对大鼠脑缺血/再灌注后DNA氧化性损伤的保护作用, 以了解电刺激小脑顶核对实验性脑缺血及再灌注后神经保护的分子机制.方法健康雄性Wistar大鼠106只, 体重(250±30)g, 随机分为4组: (1) 单纯造模组; (2) 预刺激组; (3) 毁损小脑顶核组; (4) 假手术组.毁损小脑顶核组大鼠用鹅膏氨酸毁损两侧小脑顶核, 预刺激组、毁损小脑顶核组大鼠均以电刺激器刺激左侧小脑顶核, 前3组大鼠用线栓法成功制作可复流的MCAO模型2 h后再灌注.在再灌注后6、24、48 h将大鼠断头取脑, 取第3片提取DNA或RNA.DNA样品经酶解后上高效液相-电化学检测器检测8-ohdG.RNA样品通过RT-PCR的方法探测rOOG1 mRNA的表达.结果 (1) 大鼠脑缺血/再灌注后缺血区8-ohdG堆积.预刺激组再灌注各时点的8-ohdG含量均较单纯造模组及毁损小脑顶核组减少(P＜0.01); (2) 单纯造模组及毁损小脑顶核组脑缺血/再灌注后rOGG1的转录水平相似, 再灌注后6 h其rOGG1 mRNA几乎检测不到, 随时间的延长其转录水平有所增加, 但仍较假手术组及预刺激组低(P＜0.01).预刺激组再灌注后6 h其rOGG1 mRNA的表达量与假手术组无显著性差异, 但再灌注后24及48 h其rOGG1 mRNA的表达量均较假手术组增加(P＜0.01).结论 (1) 大鼠脑缺血/再灌注后脑缺血区存在DNA氧化性损伤; (2) 预电刺激小脑顶核减少缺血区神经元凋亡可能与DNA修复酶活性上调有关.     

电刺激小脑顶核诱导脑缺血大鼠miRNAs的差异表达谱

目的研究电刺激小脑顶核诱导脑缺血大鼠miRNAs的差异表达谱,筛选与凋亡相关的miRNAs,探讨miRNAs调控电刺激小脑顶核诱导内源性抗凋亡的可能机制。方法将Sprague Dawley大鼠采用随机数字表法分为单纯造模组和预电刺激组(即电刺激小脑顶核1 h,24 h后制作右侧局灶性脑缺血模型);两组均缺血2 h后再灌注,并按再灌注时间不同分为3 h、6 h、12 h、24 h、72 h亚型(各10只)。通过微阵列芯片分析表达结果。结果电刺激小脑顶核后miR-29c、miR-494等表达水平下调,其中miR-29c差异最大,降低了近3倍(P<0.05)。同时通过生物信息学分析这些表达差异的miRNAs的靶基因,发现了几个凋亡基因相关的miRNAs,如miR-29c。结论电刺激小脑顶核可以诱导脑缺血再灌注大鼠miRNAs表达差异,一些差异表达的miRNAs与凋亡相关。     

依达拉奉对脑出血大鼠脑代谢的改善作用及其机制研究

目的探讨自由基清除剂依达拉奉对脑出血大鼠脑组织葡萄糖代谢率及神经行为学的影响,并通过检测血肿周围脑含水量及细胞凋亡水平变化,探索依达拉奉改善脑出血后脑代谢水平的作用机制。方法采用自体血立体定向注射建立大鼠脑出血模型,治疗组于建模后皮下注射依达拉奉10 mg/(kg·3 d),对照组注射同体积生理盐水。各组分别于造模后3 d行神经行为学评分及脑含水量测定,并采用小动物正电子发射断层显像/X线计算机体层成像(PET/CT)检测血肿周围葡萄糖代谢率变化,脑组织切片行原位末端脱氧核苷酸转移酶介导的生物素脱氧尿嘧啶核苷酸缺口末端标记法(TUNEL)染色,判定血肿周围细胞凋亡水平变化。结果依达拉奉干预脑出血大鼠后3 d,前肢抬起及转角实验较对照组均明显改善,脑含水量亦明显降低。依达拉奉组血肿周围脑组织葡萄糖代谢率较对照组明显改善,脑代谢降低区域体积较对照组明显减少。血肿周围脑组织TUNEL染色显示,依达拉奉组凋亡细胞明显少于对照组。结论依达拉奉可明显改善脑出血大鼠脑代谢水平及神经功能障碍,减轻脑出血后继发性损伤,其机制可能与减轻血肿周围脑水肿、抑制神经细胞凋亡有关。     

电刺激对大鼠缺血性脑卒中的保护作用

目的探讨皮层电刺激对大鼠永久性缺血性脑卒中的保护作用。方法雄性sD大鼠随机分成对照组和实验组。实验组根据刺激频率不同分成2Hz组,20Hz组,100Hz组,100／2Hz组。建立永久性梗塞模型。梗塞3h后,电极植入右侧大脑缺血区皮层进行刺激。分别在梗塞5h和24h进行行为学评分。在梗塞24h行2％氯化三苯基四氮唑溶液染色测量脑梗死比。于刺激结束1h后取脑组织Westernblot分析脑源性神经营养因子（BDNF）和血管内皮生长因子（VEGF）表达量的变化。结果2Hz电刺激组在梗死比的减少及行为学评分的改善方面最显著（均P〈0．05）。VEGF的表达量下降,而BDNF表达水平较其他各组无显著性差异。结论对于脑缺血溶栓未通患者,皮层电刺激对脑缺血可能有保护作用。     

脑出血大鼠血肿周围脑组织白细胞和凋亡细胞变化及其与脑组织含水量的关系

目的 探讨脑出血大鼠血肿周围脑组织白细胞和凋亡细胞变化及其与脑组织含水量的关系.方法 48只大鼠采用自体不凝血注入法制备脑出血模型,随机分为8组:假手术组、脑出血6h组、脑出血12h组、脑出血24h组、脑出血48 h组、脑出血72 h组、脑出血1周组和脑出血2周组.分别在相应时间点断头取脑,进行脑组织含水量测定和HE染...     

电刺激小脑顶核对大鼠局灶性脑缺血／再灌注后Ku70表达影响的研究

目的:研究预电刺激小脑顶核对大鼠脑缺血再灌注后Ku70 mRNA的表达及其神经保护的分子机制。方法:Wistar大鼠通过原位杂交的方法及末端标记法检测Ku70 mRNA的表达及Tunel阳性细胞数。结果:①单纯造模组及毁损小脑顶核组缺血/再灌注后各时点Ku70 mRNA的表达无显著性差异,均较预刺激组及假手术组明显减少(P<0.01),预刺激组除缺血/再灌注后6h Ku70mRNAR的表达较假手术组减少(P<0.01)外,余时点与假手术组Ku70 mRNA表达无明显差异;②预刺激组Tunel阳性细胞数较未给预电刺激的两组明显减少(P<0.01)。结论:①预电刺激小脑顶核能减少缺血区神经元凋亡可能与DNA修复酶Ku70活性上调有关;②毁损小脑顶核后电刺激对脑缺血/再灌注引起的氧化性DNA损伤无保护作用。     

脑血肿周围细胞间黏附分子-1 mRNA表达及白细胞浸润的实验研究

目的　探讨大鼠脑血肿周围细胞间黏附分子 1(ICAM 1)mRNA表达及白细胞浸润情况 ,明确脑血肿周围是否存在急性炎性反应。方法　胶原酶Ⅶ型脑立体定向注射制作脑出血模型 ,应用逆转录聚合酶链(RT PCR)技术检测ICAM 1mRNA表达 ;通过测定髓过氧化物酶 (MPO)活性来检测中性粒细胞的浸润情况。结果　脑出血后 6hICAM 1mRNA表达开始增加 (P <0 0 5 ) ,2 4h达高峰 (P <0 0 1) ,然后逐渐减退。脑出血后 2 4hMPO活性明显增加 (P <0 0 5 ) ,4 8h达高峰 (P <0 0 1) ,然后逐渐减退。结论　脑血肿周围存在明显的炎性反应 ,它可能参与了脑出血后周围组织的继发性损伤     

实验性脑出血血肿周围血流量变化的研究

目的　建立实验性脑出血的动物模型 ,探讨血肿周围的脑血流量变化。方法　采用犬脑内缓慢注入非肝素化自体血的方法建立实验性脑出血动物模型。用 1 4C- iodoantipyrine微示踪技术测定实验性脑出血 6 h、2 4 h、72 h血肿周围皮质、白质及对侧相应部位的脑血流量。结果　注血 6 h组、2 4 h组血肿周围白质的 CBF与对照组相比有所下降 ,但无统计学差异 ;而注血 72 h组血肿周围白质的 CBF较对照组降低了 19.8% (P<0 .0 5 ) ;注血 72 h组血肿对侧相应部位白质的 CBF较对照组升高了 14 .8% (P<0 .0 5 )。结论　犬脑内缓慢注入非肝素化自体血可建立可靠、重复性好的实验性 ICH动物模型 ,脑出血后 72 h,血肿周围白质的血流量下降 ,脑出血早期的脑损伤非缺血所致。     

脑出血大鼠血肿周围脑组织含水量与基质金属蛋白酶-9、组织基质金属蛋白酶抑制剂-1及谷氨酸表达水平的关系

目的 探讨脑出血大鼠血肿周围脑组织含水量与基质金属蛋白酶-9(MMP-9)、组织基质金属蛋白酶抑制剂-1(TIMP-1)及谷氨酸表达水平的关系.方法 雄性Wistar大鼠48只,随机分为正常对照组(n=8)、假手术组(n=8)、脑出血组(n=32),脑出血组又分为脑出血后12h、24h、72 h、7d4个亚组,每亚组8只大鼠.采用自体血尾状核注入法制备脑出血模型.采用干湿重法测定脑含水量,免疫组化法检测血肿周围脑组织MMP-9、TIMP-1及谷氨酸的表达.结果 脑出血组各时间点亚组大鼠血肿周围脑组织含水量与MMP-9、TIMP-1及谷氨酸表达水平均显著高于正常对照组和假手术组(均P＜0.01).脑出血组中,72 h亚组大鼠脑组织含水量及MMP-9、TIMP-1表达水平最高(P ＜0.01);24 h亚组大鼠脑组织谷氨酸表达水平最高(P＜0.01).多重线性回归分析结果显示,脑组织含水量(Y)与脑组织MMP-9(X1)及谷氨酸(X3)表达水平呈直线关系,多元回归方程为Y=68.894+0.281X1-0.052X3.结论 脑出血后血肿周围组织含水量及MMP-9、TIMP-1、谷氨酸的表达水平明显增高,MMP-9、谷氨酸在脑出血后血肿周围组织水肿的发生发展中具有重要作用.     

实验性脑出血急性期灶周组织水肿及炎性细胞因子的表达

目的 研究脑出血血肿周围脑组织炎性细胞因子的表达,探索其动态变化规律及与脑水肿的关系.方法 采用Wistar大鼠脑内缓慢注入自体血的方法建立实验性脑出血动物模型;随机分为6组,测定实验性脑出血6h、12h、24h、3d、5d、7d时间点血肿周围脑组织的含水量;应用免疫组化法及免疫印迹法(Western Blot)观察血肿周围脑组织中细胞因子IL-6、TNFα的表达.结果 脑出血后血肿周围脑组织的含水量逐渐增加,于3d达高峰;免疫组化染色显示血肿周围组织中神经细胞、血管内皮细胞均有IL-6及TNFa的阳性表达.免疫印迹半定量分析显示脑出血后6h血肿周围脑组织中即可见IL-6、TNFα较高水平的表达,24h达高峰,此后逐渐下降.结论脑出血急性期(6h)II-6及TNFα参与了血肿周围脑组织的损伤过程.IL-6变化曲线与脑水肿曲线呈现出一致性,推测其参与了血肿周围水肿的形成.     

PAF受体拮抗剂对缺血/再灌注脑损害的作用研究

目的血小板活化因子(platelet activating factor，PAF)与缺血／再灌注(ischemic reperfusion，IR)脑损害有密切关系，此研究拟用PAF受体拮抗剂WEB2086对PAF、炎性细胞浸润及一氧化氮(NO)在脑IR损害中的作用和机制进行探讨。方法采用线栓法制成大鼠大脑中动脉IR模型，对IR脑组织NO含量、局部脑血流量(rCBF)、中性白细胞髓过氧化物酶(MPO)及脑梗死体积进行测定。结果：PAF受体拮抗剂WEB2086对IR脑组织NO的产生有明显影响．且可明显改善IR脑组织的rCBF和显著降低MPO活性，最终减轻局部IR脑损害。结论PAF受体拮抗剂WEB2086对IR脑组织的保护作用与NO有关。     

NOS抑制剂对缺血再灌注脑组织rCBF及白细胞浸润的影响研究

目的应用非选择性NOS抑制剂L－NAME和选择性iNOS抑制剂AG治疗鼠大脑中动脉缺血再灌注损伤。通过对脑梗死体积、rCBF和白细胞浸润程度的观察，研究探讨不同类型NOS抑制剂治疗脑梗死的机制。方法采用线检法制作鼠大脑中动脉缺血再灌注模型，不同缺血及再灌注时间测定脑梗死体积、rCBF、缺血脑组织MPO酶活性。结果应用L－NAME（15mg／kg，ip）不但阻碍再灌注后rCBF的恢复，也增加缺血脑组织MPO酶活性（中性白细胞浸润增加），致脑梗死体积增加，脑损害加重；而AG（150mg／kg，ip）可有效降低脑梗死体积，且不影响rCBF的恢复和中性白细胞浸润。结论早期过度抑制神经元和内皮细胞NO对血流量的调节和抗白细胞粘附浸润作用可能是L-NAME加重缺血再灌注脑损害的重要原因之一，而选择性iNOS抑制剂有确切的脑保护作用。     

Atorvastatin Pretreatment Attenuates Ischemic Brain Edema by Suppressing Aquaporin 4

Background: Cerebral edema, a serious complication of acute cerebral infarction, has a crucial impact on morbidity and mortality in the early stage of cerebral infarction. And aquaporin 4 (AQP4), a bidirectional water transporting protein, plays a pivotal role in edema formation. At experimental model, it has proven that atorvastatin could exert pleiotropic neuroprotection on acute cerebral infarction independent of its cholesterol-lowering action. It was a common protective manifestation that atorvastatin can reduce the infarct volume and cerebral edema. However, little is known about atorvastatin improving ischemic brain edema by regulating AQP4 expression. This study intended to investigate the neuroprotection effects of atorvastatin pretreatment in rats with cerebral ischemia and further explore the potential relationship between atorvastatin and AQP4 expression. Methods: Fifty-one adult male Sprague Dawley rats were randomly divided into 3 groups: sham, middle cerebral artery occlusion (MCAO), and atorvastatin pretreatment (Ator) group. For Ator group, 20 mg/kg of atorvastatin injectable suspension was administered once for 7days by gavage before operation, whereas the others were administered the same volume of saline matching. Except for sham group, MCAO and Ator groups were subjected to permanent MCAO by modified intraluminal suture method. Infarct volume, neurological deficit, brain water content (BWC), immunohistochemistry, western blot, and polymerase chain reaction (PCR) were measured at 24 hours after MCAO. Results: Compared with sham group, the mNSS, infarct volume, and BWC of ischemic hemisphere were significantly increased (P < 0.001) in MCAO group. Positive cells and protein levels of p-p38MAPK and AQP4 in peri-infarction were significantly increased (P < 0.01). The mRNA levels of p38MAPK and AQP4 were also prominently upregulated (P < 0.01). Interestingly, preadministration of atorvastatin dramatically decreased infarct volume and the BWC of ischemic hemisphere compared with MCAO group (P < 0.05). The overexpressions of p-p38MAPK and AQP4 in peri-infarction were significantly decreased (P < 0.05) and their mRNA levels were downregulated by atorvastatin pretreatment (P < 0.05). Neurological deficits were also dramatically improved (P < 0.001). Conclusion: To the best of our knowledge, this is the first study that demonstrates an effect of atorvastatin on expression of AQP4, and we propose that decreased AQP4 expression through a p38MAPK-suppression pathway may be the mechanism of atorvastatin alleviating ischemic cerebral edema.     

脑缺血再灌流时补阳还五汤提取物对白细胞浸润及脑梗死体积的影响

目的　观察补阳还五汤提取物 (BDE)对大鼠脑缺血再灌流区白细胞浸润及脑梗死体积的影响。方法　建立大鼠大脑中动脉栓塞 (MCAO)及再灌流模型 ,利用MPO活性测定白细胞浸润和TTC染色测定脑梗死体积。结果　BDE 1组、BDE 2组MPO活性均显著低于对照组 (P <0 .0 1) ;BDE 1组、BDE 2组脑梗死体积百分比与对照组相比较 ,均有显著差异 (P <0 .0 5 )。结论　BDE可明显减轻大鼠脑缺血再灌流区白细胞浸润程度及缩小脑梗死体积。     

大鼠脑出血后脑血流和脑水分含量变化的研究

研究大鼠脑出血后局部脑血流量（ｒＣＢＦ）与脑水分变化的规律及影响因素。用立体定向法自体血回注建立大鼠脑尾状核出血模型，分别在２４ｈ内不同时限用氢清除法测定ｒＣＢＦ，干湿重法测定脑水分含量，发现出血后１０ｍｉｎ同侧ｒＣＢＦ即下降，１ｈ达最低水平，出血量大时对侧半球也有明显下降；双侧脑水分含量均明显增加，其高峰期晚于ｒＣＢＦ的下降。说明脑出血后迅速出现广泛的低灌注和脑水肿     

D1和D2受体拮抗剂对乙灶性脑缺血梗塞体积及脑血流的影响

目的 研究多巴胺（ＤＡ）Ｄ１受体拮抗剂ＳＣＨ－２３３９０和Ｄ２受体拮抗剂Ｅｔｉｃｌｏｐｒｉｄｅ对可逆性乙灶性脑缺血梗塞体积及皮层半暗带脑血流的影响。方法 采用激光多普勒脑血流计测量大鼠可逆性乙灶性脑缺血各时相皮层半暗带脑血流,并于缺血后２４小时断头取脑切片,ＴＴＣ染色,计算机图样分析系统测量脑梗塞体积。结果 Ｄ１受体拮抗剂ＳＣＨ－２３３９０可明显缩小局灶性脑缺血梗塞体积,改善缺血期各时相皮层半暗带     

尤瑞克林对大鼠局灶性脑缺血再灌注损伤后炎性反应的影响

目的研究尤瑞克林对大鼠局灶性脑缺血再灌注损伤后炎性反应的影响。方法将90只SD大鼠随机分为3组:假手术组,对照组,治疗组。采用线栓法建立大鼠大脑中动脉闭塞再灌注模型,缺血2 h后,拔出线栓,恢复灌注24 h,观察大鼠神经功能缺损症状、脑梗死体积、脑组织中白细胞浸润、MPO活性、IL-1和ICAM-1的表达。结果 (1)假手术组大鼠在神经功能缺损评分、脑梗死体积均低于对照组,有显著的统计学差异(P<0.01);脑组织中白细胞浸润程度、髓过氧化物酶(MPO)活性、ICAM-1和IL-1的表达均较对照组低,统计学差异明显(P<0.01);(2)治疗组与对照组相比,大鼠的神经功能缺损评分低、脑梗死体积小,有显著统计学差异(P<0.01);白细胞浸润程度、MPO活性、ICAM-1和IL-1的表达均较对照组减少(P<0.01)。结论尤瑞克林可通过抑制大鼠脑缺血再灌注损伤后的炎性反应来实现其神经保护作用。     

ADAMTS13 gene deletion enhances plasma high-mobility group box1 elevation and neuroinflammation in brain ischemia–reperfusion injury

Highly adhesive glycoprotein von Willebrand factor (VWF) multimer induces platelet aggregation and leukocyte tethering or extravasation on the injured vascular wall, contributing to microvascular plugging and inflammation in brain ischemia–reperfusion. A disintegrin and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) cleaves the VWF multimer strand and reduces its prothrombotic and proinflammatory functions. Although ADAMTS13 deficiency is known to amplify post-ischemic cerebral hypoperfusion, there is no report available on the effect of ADAMTS13 on inflammation after brain ischemia. We investigated if ADAMTS13 deficiency intensifies the increase of extracellular HMGB1, a hallmark of post-stroke inflammation, and exacerbates brain injury after ischemia–reperfusion. ADAMTS13 gene knockout (KO) and wild-type (WT) mice were subjected to 30-min middle cerebral artery occlusion (MCAO) and 23.5-h reperfusion under continuous monitoring of regional cerebral blood flow (rCBF). The infarct volume, plasma high-mobility group box1 (HMGB1) level, and immunoreactivity of the ischemic cerebral cortical tissue (double immunofluorescent labeling) against HMGB1/NeuN (neuron-specific nuclear protein) or HMGB1/MPO (myeloperoxidase) were estimated 24 h after MCAO. ADAMTS13KO mice had larger brain infarcts compared with WT 24 h after MCAO (p < 0.05). The rCBF during reperfusion decreased more in ADAMTS13KO mice. The plasma HMGB1 increased more in ADAMTS13KO mice than in WT after ischemia–reperfusion (p < 0.05). Brain ischemia induced more prominent activation of inflammatory cells co-expressing HMGB1 and MPO and more marked neuronal death in the cortical ischemic penumbra of ADAMTS13KO mice. ADAMTS13 deficiency may enhance systemic and brain inflammation associated with HMGB1 neurotoxicity, and aggravate brain damage in mice after brief focal ischemia. We hypothesize that ADAMTS13 protects brain from ischemia–reperfusion injury by regulating VWF-dependent inflammation as well as microvascular plugging.     

Polymorphonuclear leukocyte infiltration into cerebral focal ischemic tissue: myeloperoxidase activity assay and histologic verification.

Two different techniques were utilized to identify the infiltration of polymorphonuclear leukocytes (PMN) into cerebral tissue following focal ischemia: histologic analysis and a modified myeloperoxidase (MPO) activity assay. Twenty-four hours after producing permanent cortical ischemia by occluding and severing the middle cerebral artery of male spontaneously hypertensive rats, contralateral hemiparalysis and sensory-motor deficits were observed due to cerebral infarction of the frontal and parietal cortex. In hematoxylin-and-eosin-stained histologic sections, PMN, predominantly neutrophils, were identified at various stages of diapedesis from deep cerebral and meningeal vessels at the periphery of the infarct, into brain parenchyma. When MPO activity in normal brain tissue was studied initially, it could not be demonstrated in normal tissues extracted from non-washed homogenates. However, if tissue was homogenized in phosphate buffer (i.e., washed), MPO activity was expressed upon extraction. Utilizing this modified assay, MPO activity was significantly increased only in the infarcted cortex compared to other normal areas of the brain. This was observed in non-perfused animals and after perfusion with isotonic saline to remove blood constituents from the vasculature prior to brain removal. The increased PMN infiltration and MPO activity were not observed in forebrain tissue of sham-operated control rats. Also, MPO activity was not increased in the ischemic cortex of MCAO rats perfused immediately after middle cerebral artery occlusion, indicating that blood was not trapped in the ischemic area. By using a leukocyte histochemical staining assay, activity of peroxidases was identified within vascular-adhering/infiltrating PMN in the infarcted cortex 24 hr after focal ischemia. An evaluation of several blood components indicated that increased MPO activity was selective for PMN. The observed increase of approximately 0.3 U MPO/g wet weight ischemic tissue vs. nonischemic cerebral tissues probably reflects the increased vascular adherance/infiltration of approximately 600,000 PMN/g wet weight infarcted cortex 24 hr after focal ischemia. This combined biochemical and histological study strongly suggests that PMN adhere within blood vessels and infiltrate into brain tissue injured by focal ischemia and that the associated inflammatory response might contribute to delayed progressive tissue damage in focal stroke. This modified MPO assay is a useful, quantitative index of PMN that can be utilized to elucidate the potential deleterious consequences of neutrophils infiltrating into the central nervous system after cerebral ischemia, trauma, or other pro-inflammatory stimuli.     

l-Arginine ameliorates cerebral blood flow and metabolism and decreases infarct volume in rats with cerebral ischemia

Effects ofl-arginine, 300 mg/kg, i.p., on the regional cerebral blood flow (rCBF), brain metabolism, and infarct volume were examined in spontaneously hypertensive rats subjected to occlusion of both left middle cerebral artery and left common carotid artery. Rats treated withl-arginine had higher rCBF, determined by hydrogen clearance method, in the ischemic core (7 ± 1 ml/100 g/min, mean ± S.E.M.) and penumbral regions (16 ± 2) than did rats treated with saline (5 ± 0 and 7 ± 1, respectively). Simultaneously,l-arginine attenuated metabolic derangement in the ischemic tissue at 60 min, i.e. well maintained adenosine triphosphate (ATP) in ischemic region (1.29 ± 0.07 mmol/kg inl-arginine group vs. 1.05 ± 0.06 in saline group), and also close to normal levels in ATP (2.61 ± 0.02 mmol/kg vs. 2.45 ± 0.05), glucose (2.29 ± 0.12 mmol/kg vs. 1.80 ± 0.17) and lactate (1.63 ± 0.10 mmol/kg vs. 2.24 ± 0.21) in periischemic region. In another experiment, the effects ofl-arginine on rCBF in the subcortical regions and on infarct volume were evaluated.l-arginine, compared with saline, increased rCBF by 8 ml/100 g/min in the ischemic side and reduced infarct volume by 29% at 24 h of ischemia. These findings support thatl-arginine may be potentially useful for the treatment of acute cerebral ischemia.