银杏叶提取物对大鼠缺血再灌注皮质内氨基酸动态平衡的影响

目的 :研究不同浓度银杏叶提取物 (GBE)对大鼠缺血再灌注损伤皮质内氨基酸动态平衡的影响。方法 :将119只 Wistar大鼠随机分为 17组 ,假手术组 7只 ,缺血组 -缺血 3h组 ,缺血 3h分别再灌注 1h、2 h、 3h组各 7只 ;治疗组 (即在缺血前 30分钟给予 GBE5 mg/kg、 10 mg/kg、 15 mg/kg,腹腔给药 ) -缺血 3h、缺血 3h分别再灌注 1h、 2 h、 3h组各 7只。动物模型参照 Zivin JV的大脑中动脉线栓模型并加以改进。结果 :比较缺血组和治疗组 ,可见给予 GBE后能明显减少谷氨酸 (Glu)、天门冬安酸 (Asp)的产生 ,增加了γ-氨基丁酸 (GABA )的生成和释放 ,5 mg/kg组与 10 mg/kg、 15 mg/kg组间有显著差别 ,而后二者间无显著差别。结论 :血小板活化因子拮抗剂 GBE可通过增强抑制性氨基酸的合成、释放 ,降低兴奋性氨基酸的合成、释放来保护缺血的神经元的 ,且与用药剂量有关。     

地西泮对大鼠脑缺血再灌注损伤皮质内氨基酸含量的影响

目的 研究地西泮在脑缺血再灌注损伤中的保护作用机制。方法 将Wistar大鼠随机分为9组,假手术组7只,缺血组又分为缺血3h组、缺血3h后分别再灌注1h,2h,3h组各7只;治疗组（即在缺血前30分钟给予地西泮10mg/kg,腹腔给药）又分为缺血3h组、缺血3h后分别再灌注1h,2h,3h组各7只。动物模型参照Zivin JA大脑中动脉线栓模型并加以改进。结果 给予地西泮后能明显减少谷氨酸（Glu)和天门冬氨酸（Asp)的产生,增加r-氨基丁酸（GABA）的生成和释放。结论 地西泮可能是通过增强抑制性氨基酸的合成和释放,降低兴奋性毒性来保护缺血神经元的。     

EGb761对大鼠局灶性脑缺血再灌注损伤的保护作用

目的 :观察 EGb76 1对大鼠局灶性脑缺血再灌注损伤的保护作用。方法 :45只大鼠随机分为假手术组 (A组 ) ,脑缺血再灌注损伤组 (B组 ) ,EGb76 1治疗组 (C组 ) ,每组 15只。以线栓法制作大鼠脑缺血再灌注损伤模型。每组 10只缺血 6 0 min再灌注 6 0 min后断头处死 ,取脑测定 NO、NOS、MDA和 SOD变化 ,其余 5只缺血 3h再灌注 2 4h后断头处死 ,观察常规病理、Niss小体及凋亡细胞变化。C组于实验前 3天开始灌胃给 EGb76 1(15 0 mg/ kg,每日 2次 ,术前 1h、术后 12 h灌 EGb76 115 0 mg/ kg)。结果 :脑缺血再灌注后 ,B组 NO、MDA含量 ,NOS活性较 A组升高 ,SOD活性降低 (P<0 .0 5 ) ,病理变化明显 ,凋亡细胞增多。C组 NO、MDA含量及 NOS活性降低 ,SOD活性升高 (P<0 .0 5 ) ,C组病理变化减轻 ,凋亡细胞减少 (P<0 .0 5 )。结论 :EGb76 1对大鼠局灶性脑缺血再灌注损伤具有保护作用。     

帕瑞昔布对脑缺血损伤大鼠神经保护作用的研究

目的评价线粒体ATP敏感性钾离子通道(mitoKATP)对帕瑞昔布减轻大鼠脑缺血再灌注损伤的影响。方法成年健康雄性SD大鼠100只,体质量280~330g,随机分成5组(n=20只):假手术组(S组)、脑缺血再灌注组(I/R组)、帕瑞昔布组(P组)、5-羟葵酸组(5-HD组)和5-羟葵酸+帕瑞昔布组(5-HD+P组)。采用改良线栓法阻塞右侧颈总动脉2h恢复灌注的方法制备大鼠脑缺血再灌注损伤模型。P组在缺血前15min和再灌注12h经静脉注射帕瑞昔布,4mg/kg。5-HD组在缺血前1h经静脉注射5-HD,30mg/kg。5-HD+P组在缺血前1h经静脉注射5-HD,30mg/kg,余操作同P组。S组和I/R组给予等容量生理盐水。各组于再灌注24h时,行神经功能缺陷评分后处死取脑,检测SOD、MDA、Bcl-2及Bax蛋白表达水平。结果与S组相比,其余各组大鼠神经功能缺陷评分、MDA水平及Bax蛋白表达升高,SOD水平及Bcl-2蛋白表达降低(P0.05);与I/R组相比,P组大鼠神经功能缺陷评分、MDA水平及Bax蛋白表达降低,SOD水平及Bcl-2蛋白表达升高(P0.05);与P组相比,5-HD+P组大鼠神经功能缺陷评分、MDA水平及Bax蛋白表达升高,SOD水平及Bcl-2蛋白表达降低(P0.05)。结论mitoKATP通道参与了帕瑞昔布减轻大鼠脑缺血再灌注损伤的过程。     

银杏叶提取物对脑缺血再灌注大鼠P-选择素表达及髓过氧化物酶活性的影响

目的探讨银杏叶提取物(GBE)对缺血再灌注损伤大鼠脑组织P-选择素表达及髓过氧化物酶(MPO)活性的影响。方法将大鼠随机分为假手术组、缺血再灌注组、GBE低剂量组和GBE高剂量组;用线栓法建立局灶性脑缺血再灌注模型;GBE高、低剂量治疗组于术前30min分别给予相应剂量GBE腹腔注射,缺血再灌注组相同时点给予等量的生理盐水腹腔注射。用免疫组化法观察缺血90min再灌注24h后大鼠脑组织P-选择素表达、MPO活性变化;并进行TTC和HE染色,观察脑梗死体积及组织病理学变化。结果(1)与假手术组比较,缺血再灌注组及GBE高、低剂量组P-选择素表达和MPO活性明显增加(均P<0.05);与缺血再灌注组比较,GBE高、低剂量组P-选择素表达及MPO活性显著降低(均P<0.05);GBE高剂量组较低剂量组减少更显著(P<0.05);(2)GBE高、低剂量组和缺血再灌注组脑梗死体积分别为(109.2±9.34)mm3、(132.0±15.41)mm3和(191.6±10.92)mm3,3组间两两比较差异有统计学意义(均P<0.05);(3)GBE高、低剂量组脑组织缺血损伤病理学改变明显轻于缺血再灌注组,GBE高剂量组缺血改变亦轻于低剂量组。结论GBE通过减少P-选择素表达和中性粒细胞浸润、减轻脑缺血再灌注损伤炎症反应、缩小脑梗死体积而发挥脑保护作用,并且有剂量依赖性。     

白果内酯对高血糖大鼠脑缺血再灌注损伤的保护作用

目的 观察白果内酯对高血糖大鼠脑缺血再灌注损伤的保护作用及其可能机制.方法 采用50%的葡萄糖溶液腹腔注射(6 ml/kg)建立急性高血糖模型.采用线栓法建立大鼠脑缺血再灌注模型,按随机数字表方法将40只大鼠分为高血糖假手术组(假手术组),高血糖+缺血再灌注损伤组(模型组),高血糖+缺血再灌注损伤+白果内酯组(白果内酯组),白果内酯分三个剂量组(2.5,5,10 mg/kg),每组各8只.白果内酯组于术前3 d连续给予白果内酯腹腔注射,术前1 h再给予腹腔注射1次.脑缺血2 h,再灌注24 h后行神经功能缺损评分、脑梗死体积及脑含水量测定,同时测定脑组织中水通道蛋白-4(AQP4)mRNA的表达,超氧化物歧化酶(SOD)的活力,计算脑组织中丙二醛(MDA)的含量及去甲肾上腺素(NE)、多巴胺(DA)和5-羟色胺(5-HT)的表达.结果 白果内酯(5,10 mg/kg)组大鼠与模型组相比,神经功能缺损评分下降,脑梗死体积缩小,脑含水量降低,缺血侧脑组织中AQP4 mRNA的表达下调,SOD活力提高,MDA含量减低,NE、DA及5-HT的含量增加,差异均有统计学意义(P<0.05).结论 白果内酯对高血糖条件下的局灶性脑缺血再灌注损伤具有一定的保护作用.     

一次性酒精对缺血-再灌注大鼠神经功能及海马区GLUT-1表达的影响

目的探讨一次性给予酒精对缺血-再灌注大鼠神经功能及海马区葡萄糖转运蛋白-1(GLUT-1)表达的影响。方法将40只健康雄性Wistar大鼠随机分为酒精组24例(C组)、对照组8例(B组)、假手术组8例(A组);酒精组分为1.0g/kg组(C1)、1.5g/kg组(C2)、2.0g/kg组(C3)3个亚组,制作大脑中动脉闭塞缺血大鼠模型,缺血后行Longa 5分评分。C组于缺血-再灌注后即刻、1h、2h、3h一次性腹腔注射不同剂量(1.0g/kg、1.5g/kg、2.0g/kg)的酒精;B组一次性腹腔注射等剂量的生理盐水,缺血-再灌注后24h再行Longa 5分评分,取脑后采用免疫组化法测定大鼠缺血-再灌注脑组织海马区GLUT-1表达阳性细胞数。结果缺血-再灌注后24h与对照组比较,C组大鼠Longa评分明显减小(P<0.01),C1、C2、C3组间比较,C3组Longa评分减小最明显(均P<0.05)。C组大鼠海马区GLUT-1表达阳性细胞数明显高于B组(均P<0.01);C1、C2、C3组间比较,C2组与C3组均较C1组阳性细胞表达增多(均P<0.01);而C2组与C3组比较,GLU-1表达阳性细胞数无明显差别(P>0.05)。C组在缺血-再灌注后即刻、1h、2h、3h给予酒精,海马区GLUT-1表达阳性细胞数无明显差异(均P>0.05),但C组比B组GLUT-1表达阳性细胞数表达明显增多(P<0.01)。结论一次性给予酒精治疗可减轻缺血-再灌注大鼠神经功能缺损程度,酒精可能是通过促进神经保护因子GLUT-1的表达起到神经保护作用的。     

牛磺酸降低局灶性脑缺血引起的能量代谢紊乱和氧化损伤

目的观察牛磺酸对大鼠局灶性脑缺血引起的能量代谢紊乱和氧化损伤的影响。方法建立大鼠动脉腔内插线局灶性脑缺血模型,在缺血1h后给予牛磺酸(50mg/kg,iv),测定缺血2h再灌注22h时脑组织内ATP、乳酸和丙二醛(MDA)的含量、髓过氧化物酶(MPO)和超氧化物歧化酶(SOD)的活性及总抗氧化能力。结果牛磺酸明显降低再灌注22h时缺血脑组织内乳酸和MDA的含量及MPO活性,升高ATP的含量、SOD的活性和总抗氧化能力。结论牛磺酸可改善局灶性脑缺血损伤后的能量代谢,降低中性粒细胞的浸润,提高缺血组织的抗氧化能力,减轻局灶性脑缺血引起的过氧化损伤。     

莱菔硫烷对大鼠局灶性脑缺血再灌注损伤的保护作用及机制研究

目的 探讨莱菔硫烷对大鼠局灶性脑缺血再灌注损伤的保护作用及机制.方法 采用线栓法制备大鼠大脑中动脉阻断局灶性脑缺血模型,分别于MCAO后1h腹腔注射莱菔硫烷2.5mg/kg、5mg/kg、10mg/kg.于缺血2h再灌注24h时进行神经行为缺损评分,TTC染色评价脑梗死体积,测定脑组织中超氧化物歧化酶(SOD)活力和丙二醛(MDA)含量.免疫荧光组织化学染色法检测黄核蛋白NQ01和脂质过氧化酶Prx6的表达.结果 莱菔硫烷给药组与对照组相比均能改善大鼠脑缺血再灌注后神经行为缺损评分,减少脑梗死体积.其中5mg/kg组能显著改善大鼠脑缺血再灌注后神经行为缺损评分,减少脑梗死体积,增强SOD活性,降低MDA含量.免疫荧光组织化学染色法提示NQ01和Prx6的表达明显增强.结论 莱菔硫烷对大鼠局灶性脑缺血再灌注损伤有神经保护作用,其机制可能与上调内源性抗氧化蛋白NQ01和Prx6的表达有关.     

托吡酯对大鼠脑缺血再灌注后血清超氧化物歧化酶活性、丙二醛含量及神经功能的影响

目的探讨托吡酯(TPM)对大鼠脑缺血再灌注后血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和神经功能的影响。方法将SD大鼠随机分为缺血再灌注组、TPM组及假手术组;采用线栓法建立大鼠大脑中动脉闭塞模型,TPM组动物分别于插线和再灌注时腹腔注射TPM混悬液(8mg/ml,80mg/kg);各组术后24h时进行神经功能评分后处死动物。采用羟胺氧化法测定血清SOD活性及硫代巴比妥酸法测定血清MDA含量。结果血清SOD活性及MDA含量缺血再灌注组分别为(157.72±19.04)U/ml及(7.45±0.84)nmol/ml,TPM组分别为(171.25±15.72)U/ml及(6.10±0.98)nmol/ml,假手术组分别为(179.74±7.95)U/ml及(5.90±0.72)nmol/ml;与TPM组及假手术组相比,缺血再灌注组大鼠血清SOD活性明显降低,MDA含量明显升高(均P<0.05)。TPM组及假手术组间血清SOD活性和MDA含量差异无显著性。TPM组神经功能评分较缺血再灌注组有显著改善(P<0.05)。结论TPM能减少脑缺血再灌注大鼠脑组织中抗氧化酶的消耗,有效抑制氧自由基的产生及其毒性,具有减轻脑缺血神经功能障碍的作用。     

亚低温在急性脑缺血中对氨基酸和自由基含量的影响

目的研究亚低温状态下,急性脑缺血时皮质内四种氨基酸和自由基含量的改变,探讨亚低温对缺血脑组织的保护机制。方法将63只Wistar大鼠随机分为9组,假手术组7只,缺血组(手术后将其颞厂讥温度控制在36．5+-0．5℃)-缺血3h组,缺血3h分别再灌注1h、2h、3h组各7只;亚低温组(手术后将其颞肌温度控制在32．5±0．5℃)-缺血3h,缺血3h分别再灌注1h、2h、3h组各7只。动物模型参照Zealonga的大脑中动脉线栓模型并加以改进。结果比较缺血组和低温组,可见低温组缺血皮质内的谷氨酸(Glu)、天门冬安酸(Asp)、丙醛(MDA)的产生明显减少,而超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)的生成和释放明显增加,γ-氨基丁酸(GABA)的含量亦增加。结论亚低温状态下4种氨基酸含量及自由基系统的改变是其保护缺血神经元的重要机制。     

门冬氨酸钾对局灶性脑缺血再灌注大鼠的保护作用研究

目的 观察门冬氨酸钾对大鼠局灶性脑缺血再灌注后神经细胞凋亡的保护作用。 方法 采用雄性SD大鼠右侧大脑中动脉闭塞模型,缺血2 h,再灌注22 h。大鼠随机分为5组,每组10 只,在缺血后1 h经腹腔注射给予生理盐水（1 ml/kg）或不同剂量门冬氨酸钾（10 mg/kg、25 mg/kg、 62.5 mg/kg和125 mg/kg）,观察不同剂量门冬氨酸钾对大鼠脑缺血再灌注后神经功能缺损和梗死 体积的影响。另取32只大鼠随机分为溶剂对照组和门冬氨酸钾组,在缺血后1 h腹腔注射生理盐水 （1 ml/kg）或门冬氨酸钾（62.5 mg/kg）,同时设立假手术组16只,检测三组大鼠脑组织三磷酸腺苷 （adenosine triphosphate,ATP）和乳酸水平（每组10只）,以及凋亡性细胞情况（每组6只）。 结果 与溶剂对照组比较,62.5 mg/kg剂量的门冬氨酸钾能显著改善神经功能缺损（P <0.001）, 降低梗死体积（P =0.011）;与溶剂对照组比较,25 mg/kg剂量的门冬氨酸钾能减少梗死体积 （P =0.040）,但神经功能评分无差异;10 mg/kg和125 mg/kg剂量的门冬氨酸钾组神经功能评分和 梗死体积与溶剂对照组均无差异。与溶剂对照组比较,门冬氨酸钾（62.5 mg/kg）能减少ATP的下降 （P =0.036）和细胞凋亡（P <0.001）。 结论 门冬氨酸钾对大鼠局灶性脑缺血再灌注后的细胞凋亡有保护作用。     

NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat

Free radicals have gained wide acceptance as mediators of cerebral ischemic injury. It has previously been reported that a spin trap nitrone, alpha-phenyl-N-tert-butyl nitrone (PBN), can reduce infarct volumes in rats subjected to either permanent or transient focal cerebral ischemia. A recent study has demonstrated that NXY-059, a novel free radical trapping nitrone compound, has a neuroprotective effect against transient focal cerebral ischemia. This study was designed to determine the effect of NXY-059 in a rodent model of permanent focal cerebral ischemia. Male spontaneously hypertensive rats were subjected to permanent middle cerebral artery occlusion (MCAO) by placement of a microaneurysm clip on the middle cerebral artery (MCA). Animals were divided into three groups: (1) physiological saline given as a 1 ml/kg i.v. bolus administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 0.5 ml/h of physiological saline for 24 h (n=10); (2) 30 mg/kg, 1 ml/kg, i.v. bolus of NXY-059 dissolved in physiological saline administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 30 mg/kg/h, 0.5 ml/h, of NXY-059 for 24 h (n=9); (3) 60 mg/kg, 1 ml/kg, i.v. bolus of NXY-059 dissolved in physiological saline administered 5 min post MCAO followed immediately by a continuous i.v. infusion of 60 mg/kg/h, 0.5 ml/h, of NXY-059 for 24 h (n=12). Infarction was quantified after a survival period of 24 h. Differences in infarct volume were examined with one-way ANOVA following Dunnet's multiple comparison test. The percentage of cortical infarction in the saline control group was 22.6 +/- 6.8% (mean+/-S.D.) of contra-lateral hemisphere, and in the 30 mg/kg/h NXY-059-treated group was 17.4% +/- 6.8% (NS). Plasma concentration (microM/l) of NXY-059 in the 30 mg/kg/h group was 80.2 +/- 52.2 (n=9), while in the 60 mg/kg/h group plasma concentration (microM/l) of NXY-059 was 391.0 +/- 207.0 (n=10). Infarction in the 60 mg/kg/h NXY-059-treated group was significantly reduced (P=0.009) to 14.5 +/- 5%. Our preliminary data demonstrate that administration of NXY-059 (60 mg/kg/h for 24 h) ameliorates cortical infarction in rats subjected to permanent focal cerebral ischemia with 24 h survival.     

Glycoprotein IIb/IIIa antagonist, murine 7E3 F(ab') 2, and tissue plasminogen activator in focal ischemia: evaluation of efficacy and risk of hemorrhage with combination therapy.

Tissue hypoperfusion during cerebral ischemia results from occlusion of large and small vessels. Combination treatment strategies using fibrinolytics to thrombolyse an embolic clot and antiplatelet agents to prevent reocclusion and the formation of new platelet thrombi in the microcirculation may offer advantages over single-agent therapy. The authors report on the effects of tissue plasminogen activator (rt-PA), a glycoprotein (GP) IIb/IIIa receptor antagonist, 7E3 F(ab') 2, or a combination of the two agents in a focal embolic model of cerebral ischemia in Wistar rats. Focal ischemia was produced by introducing an autologous thrombus into the right side middle cerebral artery. Forty-six male Wistar rats were randomly divided into 6 groups: control (n = 8), 7E3 F(ab') 2 (n = 9, 6 mg/kg), rt-PA (n = 9, 10 mg/kg), rt-PA (n = 6, 20 mg/kg), and 7E3 F(ab') 2 with either 10 mg/kg (n = 10) (low-dose combination) or 20 mg/kg (n = 6) (high-dose combination) rt-PA. Evaluation of neurobehavioral scores, cerebral angiography, bleeding time, and measurement of brain infarction volume were used to determine efficacy. All actively treated groups showed a significant reduction in the infarct volume. Animals treated with 7E3 F(ab') 2 showed reduced infarction volumes (24.0 +/- 5.1%) compared with controls (42.43 +/- 5.6%, P < 0.02). Treatment with rt-PA significantly reduced infarction volume (20.7 +/- 3.3, = 0.01) at 10 mg/kg and at 20 mg/kg (19.5 +/- 8.2%, P < 0.05). Compared with vehicle-treated animals, the low-dose combination (16.4 +/- 5.5, P < 0.003) and high-dose combination (23.7 +/- 6.2%, P < 0.05) showed significant reduction in infarction volume. Cerebral angiography revealed significantly better recanalization in the combination group (5/6 animals in the high dose and 4/6 in low dose) compared with animals treated with 7E3 F(ab') 2 (3/10) or rt-PA alone (2/6). Bleeding time significantly increased from 11.25 +/- 1.9 minutes in the control group to 17 +/- 3.1 minutes in the rt-PA group, 24.5 +/- 2.6 minutes in the 7E3 F(ab') 2 group, 25.7 +/- 3.1 minutes in the low-dose combination group, and 32.5 +/- 4.7 minutes in the high-dose combination group. The incidence of intercerebral hemorrhage was highest in the high-dose combination group (6 of 6 animals) and lowest in the single treatment with 7E3 F(ab') 2 alone (1 of 10 animals) ( P < 0.05). Our data show that murine 7E3 F(ab') 2 alone has therapeutic effects when used after cerebral ischemia. Although this study suggests that higher doses of thrombolytic combined with anti-GPIIb/IIIa therapy may increases the risk of intracranial hemorrhage, the data also support the notion that anti-GPIIb/IIIa agents can safely be combined with low doses of thrombolytic agent to produce significant attenuation of neuronal damage with no increase in the incidence of cerebral hemorrhage.     

The N-methyl-D-aspartate antagonist, MK-801, fails to protect against neuronal damage caused by transient, severe forebrain ischemia in adult rats

The neuroprotective effects of dizocilipine maleate (MK-801), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor/channel, were tested in the 4-vessel occlusion rat model of forebrain ischemia. Adult Wistar rats, treated intraperitoneally with MK-801 or saline using several different treatment paradigms were subjected to 5 (n = 208) or 15 (n = 62) min of severe, transient forebrain ischemia. In saline-treated animals, 15 min of ischemia (n = 13) produced extensive and consistent loss of pyramidal neurons in the CA1 zone of hippocampus. The degree and distribution of cell loss were not reduced by single dose preischemic administration of MK-801 at 1 (n = 7), 2.5 (n = 4), or 5 mg/kg (n = 8). In other animals subjected to 15 min of forebrain ischemia, multiple doses of MK-801 (5, 2.5, and 2.5 mg/kg) given immediately and at approximately 8 and 20 hr after cerebral reperfusion (n = 5) did not alter CA1 injury compared to saline-treated controls (n = 5). Five minutes of forebrain ischemia in saline-treated animals, (n = 82) resulted in significantly fewer (p less than 0.001) dead CA1 pyramidal cells and a greater variance compared to animals subjected to 15 min of ischemia. Power analysis of the preliminary saline-treated animals subjected to 5 min of ischemia (n = 22) indicated that 60 animals per group were necessary to detect a 15% difference between MK-801 and vehicle-treated groups. Multidose treatment with MK-801 (1 mg/kg) given 1 hr prior to 5 min of ischemia (n = 60) and again at approximately 8 and 16 hr after recirculation failed to attenuate hippocampal injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term neuroprotective effect of inhibiting poly(ADP-ribose) polymerase in rats with middle cerebral artery occlusion using a behavioral assessment

Poly(ADP-ribose) polymerase (PARP) can initiate an energy-consuming and inefficient repair cycle following cerebral ischemia/reperfusion by transferring ADP ribose units to nuclear proteins eventually leading to cellular dysfunction and neuronal death. 3-Aminobenzamide (3-AB) is a selective inhibitor of PARP that can significantly reduce brain damage after focal ischemia in rats and displays a low toxicity in vivo. The goals of this study were to determine if inhibiting PARP with 3-AB has a long-term neuroprotective effect and if functional outcome improves in rats following focal ischemia and treatment with 3-AB. Focal ischemia was induced by a 2-h occlusion of the middle cerebral artery (MCA), using an intraluminal filament. Motor functions were evaluated from 5 to 28 days after reperfusion in four groups of rats: stroke without treatment; stroke treated with 3-AB at doses of 15 mg/kg, stroke treated with 3-AB at doses of 55 mg/kg; and the non-ischemic control rats. Functional behaviors were tested by a series of motor function tasks (foot placing, parallel bar crossing, rope and ladder climbing), as well as a neurological examination. Infarct volume of stroke brain in the same rat was determined by Nissl staining 28 days after surgery. Comparison of the untreated stroke group (n=11) and the treated stroke groups indicates that impairment of motor function was significantly (P<0.001) reduced by administration of 3-AB at doses of 15 mg/kg (n=9) or 55 mg/kg (n=10). Neurological outcome was also improved significantly (P<0.001). Infarct volume was significantly (P<0.01) reduced in both treated groups. Long-term neuroprotection following ischemia/reperfusion injury to the brain can be obtained by administration of a PARP inhibitor. The motor tests employed in this study can be used as sensitive, objective and reproducible measurements of functional impairment in rats following an ischemic stroke.     

Failure of levemopamil to improve histological outcome following temporary occlusion of the middle cerebral artery in cats

Levemopamil, a novel calcium channel blocker with antagonistic action on serotonin S₂-receptors has been reported to be a promising compound for therapy in cerebral ischemia. This data has been obtained in the rat only, and it is of interest to determine if these beneficial effects are present in other models of ischemia in other species. The present study was therefore designed to examine its effect on histological outcome and changes in EEG after focal cerebral ischemia and reperfusion in the cat. Focal cerebral ischemia was induced by a reversible 1 hour occlusion of the middle cerebral artery followed by reperfusion of the brain. Six hours after the induction of the insult, the brain was perfusion-fixed and evaluated for histological damage by light microscopy. In 8 animals an intravenous infusion of levemopamil was initiated 5 minutes after middle cerebral artery occlusion at a rate of 4 mg/kg/h for 15 min and then at 0.6 mg/kg/h until the end of the study. A control group (n = 7) received a similar infusion of saline. The EEG amplitude did not differ between the two groups at any point of the study. The area of ischemic damage in the sections obtained for histological examination at 1-mm intervals, as well as the total volume of ischemic damage for both groups (treated: 1.33 cm³; untreated: 0.97 cm³) also did not show any significant differences. These results indicate that postischemic treatment with levemopamil at this dose, and in this model of focal cerebral ischemia and reperfusion, does not attenuate the ischemic damage.