地西泮对大鼠脑缺血-再灌注损伤的保护作用

目的 观察地西泮对全脑缺血—再灌注损伤的保护作用。方法 采用改良的Pulsinelli四血管法建立大鼠全脑缺血模型，缺血时间为15min。动物随机分为四组：假手术组、缺血—再灌注组、地西泮治疗组和地西洋预注组。于动物存活第6天行Y—型迷宫检测大鼠的学习能力，第7天检测记忆能力并行海马CAl区组织病理学检查。结果 大鼠缺血—再灌注后学习和记忆能力明显下降，海马CAl区神经元细胞损伤，地西泮治疗组与地西泮预注组能不同程度减轻海马CAl区神经元的损伤，改善缺血—再灌注后学习和记忆的降碍。结论 一过性脑缺血能产生神经元损伤。地西泮对全脑缺血—再灌注有一定的保护和治疗作用。     

七氟醚后处理对糖尿病大鼠脑缺血-再灌注损伤的影响

目的研究七氟醚后处理对糖尿病大鼠脑缺血-再灌注损伤的影响。方法雄性SD大鼠32只,3.0~3.5月龄,体重280~320 g,采用随机数字表法分为四组:非糖尿病缺血-再灌注对照组(NDC组)、糖尿病缺血-再灌注对照组(DC组)、非糖尿病缺血-再灌注七氟醚后处理组(NDS组)和糖尿病缺血-再灌注七氟醚后处理组(DS组),每组8只。采用栓线法和链脲佐霉素制备缺血-再灌注损伤大鼠模型和糖尿病大鼠模型。缺血2 h,再灌注24 h后,进行大鼠神经缺损评分,采用TTC法测定脑梗死体积,Western blot法测定血管生成素-1(angiopoiettin-1,Ang-1)蛋白含量。结果DC组神经缺损评分、脑梗死体积百分比明显高于NDC组,Ang-1蛋白含量明显低于NDC组(P0.05);NDS组神经缺损评分、脑梗死体积百分比明显低于NDC组,Ang-1蛋白含量明显高于NDC组(P0.05);DS组神经缺损评分、脑梗死体积百分比明显低于DC组,Ang-1蛋白含量明显高于DC组(P0.05)。结论大鼠脑缺血-再灌注后,糖尿病可加重神经缺损,增大脑梗死体积,减少Ang-1蛋白含量;七氟醚可减轻神经缺损,减小脑梗死体积,增加Ang-1蛋白含量;七氟醚后处理减轻大鼠脑缺血-再灌注损伤与Ang-1蛋白含量增加有关。     

电针预处理对局灶性脑缺血再灌注大鼠皮质神经元pSTAT3蛋白表达的影响

目的 评价电针预处理对局灶性脑缺血再灌注大鼠皮质神经元磷酸化信号转导及转录激活因子3(pSTAT3)蛋白表达的影响.方法 成年雄性SD大鼠45只,体重280 ～ 320 g,采用随机数字表法,将其随机分为假手术组、局灶性脑缺血再灌注组和电针预处理组(n=15).局灶性脑缺血再灌注组采用线栓阻塞颈总动脉和颈外动脉24 h恢复灌注的方法制备大鼠局灶性脑缺血再灌注模型.电针预处理组电针刺激百会穴30 min,处理后24h时制备模型,再灌注24 h时进行神经行为学评分,随后处死大鼠取脑测定脑梗死体积,计算脑梗死体积百分比,采用免疫荧光染色和Westem blot法检测缺血半暗带皮质神经元pSTAT3蛋白的表达.结果 与假手术组比较,局灶性脑缺血再灌注组和电针预处理组神经行为学评分降低,脑梗死体积百分比增加,皮质神经元pSTAT3蛋白表达上调(P＜0.05);与局灶性脑缺血再灌注组比较,电针预处理组神经行为学评分升高,脑梗死体积百分比减少,皮质神经元pSTAT3蛋白表达上调(P＜0.05).结论 电针预处理通过上调皮质神经元pSTAT3蛋白的表达减轻大鼠局灶性脑缺血再灌注损伤.     

瘦素对小鼠脑缺血／再灌注损伤后脑血流和神经营养因子表达的影响

目的：研究瘦素（leptin）对脑缺血／再灌注损伤后血流变化和神经营养因子表达的影响。方法：45只雄性昆明小鼠随机分为假手术组、模型组和leptin治疗组,每组15只。采用大脑中动脉栓塞方法制备小鼠局灶性脑缺血／再灌注损伤模型。leptin治疗组和模型组于动脉栓塞（即缺血0min）的同时分别腹腔注射leptin 1μg／g或等体积磷酸盐缓冲液（PBS）,假手术组未行栓塞。于MCAO前、缺血2h、再灌注5min和24h采用激光多普勒流量仪检测缺血侧脑组织大脑中动脉供血区血流量变化,免疫组化染色观察神经生长因子（NGF）和脑源性神经生长因子（BDNF）的表达。结果：模型建立后,大脑中动脉分支血流速度明显减慢;再灌注24h,leptin治疗组脑组织血流量较模型组明显改善（P〈0．01）。与假手术组相比,模型组缺血半影区NGF表达水平显著升高（P〈0．01）,大部分NGF阳性细胞明显凋亡,而BDNF表达无明显升高（P〉0．05）;leptin治疗组NGF和BDNF表达水平均较假手术组显著升高（P〈0．01）,NGF和BDNF阳性细胞形态接近正常。结论：leptin能够升高神经营养因子NGF、BDNF的表达水平,增加缺血区血流量,从而在脑缺血性损伤中发挥神经保护作用。     

神经节苷脂对大脑缺血再灌注损伤的保护作用

目的　探讨神经节苷脂 (GM 1)对脑缺血再灌注损伤的神经细胞的影响。方法　仿照Pulsinelli四血管闭塞法建立大鼠全脑缺血再灌注损伤模型 ,检测外源性GM 1对脑缺血再灌注损伤后脑细胞外液乳酸及葡萄糖含量的影响。结果　急性缺血再灌注组、GM 1治疗组乳酸缺血后迅速升高 ,再灌注 3 0min达高峰 ,其后逐渐下降。再灌注组在 3 0～ 12 0min内显著高于对照组 ,治疗组在 3 0～ 90min内显著高于对照组 ,但低于再灌注组 (P <0 .0 5 )。急性缺血再灌注组、GM 1治疗组葡萄糖缺血后迅速降低 ,再灌注 3 0min达低谷 ,其后逐渐上升。再灌注组在 3 0～ 12 0min内显著低于对照组 ,治疗组在 3 0～ 90min内低于对照组 ,但显著高于再灌注组 (P <0 .0 5 )。结论　脑缺血再灌注损伤后 ,早期使用GM 1治疗 ,明显减轻脑组织中乳酸的堆积 ,增加葡萄糖含量 ,增强神经元细胞的存活。     

线粒体ATP敏感性钾通道在七氟醚预处理减轻大鼠脑缺血再灌注损伤中的作用

目的 探讨线粒体ATP敏感性钾通道(mito-K_(ATP)通道)在七氟醚预处理减轻大鼠脑缺血再灌注损伤中的作用.方法 健康雄性SD大鼠100只,体重250～300 g,随机分为5组(n=20):假手术组(S组)、缺血再灌注组(I/R组)、七氟醚预处理组(Sevo组)、mito-K_(ATP)通道阻断剂5-羟基葵酸(5-HD)组及5-HD+七氟醚预处理组(5-HD+Sevo组).采用线栓法制备大鼠局灶性脑缺血再灌注模型,七氟醚预处理方法:吸入2.4%七氟醚60 min后吸入纯氧洗脱15 min,停止吸入七氟醚后24 h时制备脑缺血再灌注模型.分别于再灌注6、24 h时进行神经功能损伤评分,计算脑梗死体积百分比,采用Western blot法测定蛋白激酶Cε(PKCε)膜转位水平.结果 与S组比较,其余各组大鼠再灌注6、24 h时神经功能损伤评分升高,脑梗死体积百分比及脑组织PKCε膜转位水平升高(P<0.05);与I/R组、5-HD组及5-HD+Sevo组比较,Sevo组大鼠再灌注6、24 h时神经功能损伤评分降低,脑梗死体积百分比降低,再灌注6 h时脑组织PKCε膜转位水平升高(P<0.05).结论 mito-K_(ATP)通道介导了七氟醚预处理减轻大鼠局灶性脑缺血再灌注损伤的作用,其机制可能与调控PKCε膜转位有关.     

七氟醚预处理对大鼠局灶性脑缺血-再灌注损伤的保护作用

目的观察七氟醚预处理对大鼠局灶性脑缺血一再灌注损伤的保护作用。方法32只雄性SD大鼠随机均分为四组,假手术组：仅分离血管,不留置线栓;Sevol、Sevo2和对照组：分别在缺血前吸入2％、3％七氟醚和纯氧30min。用左颈内动脉尼龙线线栓法使大脑中动脉阻闭120min,拔出尼龙线恢复再灌注。观察再灌注24h后神经功能损害改变并评分,然后处死动物取大脑行2,3,5-氯化三苯基四氮唑（TTC）染色以测量脑梗死体积。结果缺血-再灌注损伤后对照组大鼠神经功能损害较Sevol和Sevo2组更明显（P〈0．05或P〈0．01）。缺血-再灌注损伤24h后Sevo1组和Sevo2组脑梗死体积和梗死体积百分比,较对照组减小（P〈0．01）。结论缺血前吸入2％、3％七氟醚对大鼠局灶性脑缺血-再灌注损伤可产生保护作用。     

异氟醚预处理对局灶性脑缺血再灌注损伤大鼠缺血半暗带TLR4-MyD88信号通路的影响

目的 探讨异氟醚预处理对局灶性脑缺血再灌注损伤大鼠缺血半暗带TLR4-MyD88信号通路的影响.方法 成年雄性SD大鼠54只,体重250 ～ 280 g,采用随机数字表法,将其随机分为3组(n=18):假手术组(S组)、脑缺血再灌注组(I/R组)和异氟醚预处理组(IP组).S组仅分离血管不留置线栓;I/R组采用线栓法制备右侧局灶性脑缺血再灌注损伤模型,缺血2h,再灌注24 h;IP组吸入2.0％异氟醚2h,预处理结束后24h时制备右侧局灶性脑缺血再灌注损伤模型.于再灌注24 h时行神经功能缺陷评分,随后处死大鼠,每组随机抽取5只大鼠,取脑组织,测定脑梗死体积,采用Westernblot法和RT-PCR法检测大鼠右侧脑缺血半暗带区HSP60、TLR4、MyD88蛋白及mRNA的表达情况;每组剩余的3只大鼠,采用TUNEL法检测大鼠右侧脑缺血半暗带区细胞凋亡情况.结果 与S组比较,I/R组和IP组神经功能缺陷评分升高,脑梗死体积增大,右侧脑缺血半暗带区凋亡指数升高,HSP60、TLR4、MyD88蛋白及mRNA表达均上调(P＜0.05);与I/R组比较,IP组神经功能缺陷评分降低,脑梗死体积减小,右侧脑缺血半暗带区凋亡指数降低,HSP60、TLR4、MyD88蛋白及mRNA表达均下调(P＜0.05).结论 异氟醚预处理可保护脑缺血再灌注大鼠缺血半暗带,其机制可能与抑制大鼠脑缺血半暗带TLR4-MyD88信号通路有关.     

Box-siRNA预先给药对大鼠脑缺血再灌注损伤的作用

目的探讨B细胞淋巴瘤相关X蛋白基因-双链RNA（Bax-siRNA）对大鼠脑缺血再灌注损伤的作用。方法SD大鼠66只，体重290～310g，随机分成3组：假手术组（S组，n=6）、局灶性脑缺血再灌注组（C组，n=30）、局灶性脑缺血再灌注＋Bax—siRNA组（B组，n=30）。C组、B组行大脑中动脉阻断，阻断1h再开放，制备大鼠局灶性脑缺血再灌注模型，B组在缺血前即刻、16、24h水压法尾静脉注射Bax-siRNA 2．5mg／kg（用PBS稀释至10ml），C组给予等量PBS，S组只作切口，不作缺血再灌注。B组、C组分别于再灌注1、5、11、23、47h各处死6只大鼠，S组实验后23h处死大鼠，断头取脑，计算脑梗塞体积比，用RT-PCR法测定脑缺血半影区Bax mRNA表达水平。结果B组、C组再灌注11h时脑梗塞体积比达到高峰，再灌注23h时B组、C组脑梗塞体积比均高于S组（P〈0．01）；与C组比较，B组脑梗塞体积比缩小（P〈0．05）。S组和B组Bax mRNA无表达，C组再灌注23h时Bax mRNA表达强于S组。结论Bax-siRNA预先给药可减轻大鼠脑缺血再灌注损伤。     

麻醉剂量异丙酚对大鼠脑缺血/再灌注损伤的保护作用

目的：研究异丙酚对脑缺血／再灌注损伤的保护作用,方法采用改良Longa法制成大鼠脑缺血／再灌模型,随机分为模型组、异丙酚组、 尼莫地平组对照组,观察麻醉剂量的异丙酚对脑缺血／再灌注损伤的保护作用并研究其机制。结果：麻醉剂量的异丙酚能明显降低大鼠局灶性脑缺;知／再灌注死亡率,明显缩小脑梗范围,抑制脑缺血／再灌注后血清乳酸脱氢产肌酸激酶的升高程度,改善电镜下细胞超微结构的损害,明显升高脑组织超氧化物歧化酶的活性,减少脑组织细胞内钙离子含量,减少丙二醛的生成,结论麻醉剂量的异丙酚对大鼠局灶性脑缺血再灌注损伤具有保护作用,其机制与抑制钙离子超载和抑制脂质过氧化反应有关。     

Effects of the calcium antagonist nilvadipine on focal cerebral ischemia in spontaneously hypertensive rats

We studied the efficacy of preischemic and postischemic systemic treatment with a new calcium antagonist nilvadipine in a permanent focal cerebral ischemia model of spontaneously hypertensive rats. Rats that underwent microsurgical middle cerebral artery occlusion were blindly assigned to a single intraperitoneal injection of nilvadipine (0.32 mg/kg) or the same amount of polyethylene glycol either 15 minutes before, immediately after, 1 hour after, or 3 hours after occlusion of the left middle cerebral artery. Neurologic conditions of rats were closely examined, and rats were killed 24 hours later. Removed brains were sliced coronally, stained with triphenyltetrazolium chloride, and the size of infarct was determined. Although no neurologic improvements were observed in the treated rats, the area of infarcts was significantly reduced in the groups treated before, immediately after, and 1 hour after occlusion of the middle cerebral artery. Treatment started 3 hours after occlusion was ineffective.     

Induction of tolerance against ischemia/reperfusion injury in the rat brain by preconditioning with the endotoxin analog diphosphoryl lipid A

OBJECT: Inflammatory responses and oxygen free radicals have increasingly been implicated in the development of ischemic brain injury. In some cases, an attenuation of inflammation or free-radical injury can provide tissue protection. Diphosphoryl lipid A (DPL) is a detoxified derivative of a lipopolysaccharide (endotoxin) of Salmonella minnesota strain R595, which is capable of stimulating the immune system without eliciting direct toxic effects. In this study the authors examined the influence of preconditioning with DPL on ischemia/reperfusion injury in rats. METHODS: Sprague-Dawley rats were injected intravenously with either DPL or vehicle. Twenty-four hours later, some animals were tested for superoxide dismutase (SOD) activity. Others were subjected to a 3-hour period of focal cerebral ischemia and, after a reperfusion period of 24 hours, were killed. Infarction volume, SOD activity, and myeloperoxidase (MPO) activity were assayed in the postischemic animals. Pretreatment with DPL produced significant reductions in cerebral infarction and MPO activity in the ischemic penumbra. A significant enhancement of basal SOD activity was observed 24 hours after DPL treatment (that is, before ischemia), and a further enhancement of SOD activity was seen in the ischemic penumbra 24 hours after reperfusion. CONCLUSIONS: These data provide the first evidence of a neuroprotective effect of preconditioning with DPL in an in vivo model of cerebral ischemia. Although the precise mechanisms through which DPL exerts its neuroprotective influence remain to be established, an inhibition of the complex inflammatory response to ischemia and an enhancement of endogenous antioxidant activity are leading candidates.     

Autotransplantation of peripheral cholinergic neurons into the brains of Alzheimer model rats

Summary Current hypotheses regarding Alzheimer's disease implicate cholinergic function. In this study, peripheral cholinergic neurons in the vagal nodosal ganglion were transplanted into the brains of Alzheimer model rats. Eighteen Sprague-Dalwey strain rats were divided into three groups: 1) unoperated control rats, 2) rats that had undergone bilateral destruction of the nucleus basalis of Meynert (NBM) (Alzheimer model), and 3) the transplantation group in which the vagal nodosal ganglion was transplanted into the cerebral neocortex one week after the bilateral destruction of the Meynert nucleus. Seven weeks after the transplantation rat behaviour was assessed using psychological tests (spontaneous activitiy, passive avoidance response and the Hebb-Williams maze test). The Alzheimer model rats had a statistically significant increase in spontaneous activity in comparison with controls (P<0.01). The transplant rats showed some amelioration of this abnormal increase in spontaneous activity observed in the Alzheimer model rats. All of the control rats showed conditioned passive avoidance responses, while only one Alzheimer model rat retained is shocked-conditions behaviour before 24 hours (P<0.01). Three of the six transplanted rats showed complete improvement in the passive avoidance response test. In the Hebb-Williams maze test, the rats with NMB lesions made more errors than the control rats. The transplanted rats had a lower number of errors than NBM-lesioned rats but still more than the controls. Histological examination revealed many cholinergic cells in the transplanted tissue, especially in the area adjacent to the cerebral cortical surface.The present results indicate that autotransplantation of peripheral cholinergic cells ameliorates abnormal behaviour in Alzheimer model rats.     

Role of a synthetic pyrimidine compound,MS-818, in reduction of infarct size and amelioration of sensorimotor dysfunction following permanent focal cerebral ischemia in rats

OBJECT: A synthetic heterocyclic pyrimidine compound, MS-818 (2-piperadino-6-methyl-5-oxo-5,6-dihydro-(7H) pyrrolo-[3,4-d] pyrimidine maleate) is reported to have a variety of biological activities including neurite outgrowth, astrocyte differentiation, suppression of neuronal apoptosis, regeneration of injured peripheral nerves, fracture repairs, angiogenesis, and superovulation. To be able to explicate the neurotrophic effects of MS-818, the authors evaluated its effect on the reduction of infarct volume and amelioration of sensorimotor dysfunction in a rat model of focal ischemia. METHODS: Forty male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion and assigned to one of four treatment groups (10 animals in each group). The MS-818 (1, 5, or 10 mg/kg) or phosphate-buffered saline (control group) was administered intraperitoneally at onset of ischemia and again 24 hours later. The rats were killed 48 hours after they underwent surgery to induce stroke, and infarct volume was determined using an image-analysis computer software program following staining with 2,3,5-triphenyltetrazolium chloride. Postischemic neurological deficit and body weight were also assessed. CONCLUSIONS: Significant reductions in infarct volume (total and cortical infarction) were found in all the MS-818-treated groups compared with the control group. Furthermore, MS-818 induced significant amelioration of sensorimotor dysfunction, as indicated by the results of forelimb and hindlimb placing tests. The present findings suggest that MS-818, which has a much smaller molecular weight than neurotrophic peptides. represents a new approach to the treatment of focal cerebral ischemia.     

Effect of opiate antagonists on middle cerebral artery occlusion infarct in the rat

The authors examined the effect of the opiate antagonists naloxone and thyrotropin-releasing hormone (TRH) on neurological outcome and the size of areas of cerebral infarction in a rat model of focal cerebral ischemia. The middle cerebral artery (MCA) was permanently occluded in 66 adult Sprague-Dawley rats. The rats were randomly divided into three groups. In 20 Group I rats, TRH in normal saline was administered initially as a 2-mg/kg bolus followed by continuous infusion of 2 mg/kg/hr for 4 hours. In 20 Group II rats, naloxone in normal saline was administered initially as a 2-mg/kg bolus followed by continuous infusion of 2-mg/kg/hr for 4 hours. In 26 Group III rats, physiological saline was administered as an initial 0.5-cc bolus followed by continuous infusion of 0.5 cc/hr for 4 hours. All solutions were given in volumes of 0.5 cc for the bolus and 0.5 cc/hr for continuous infusion, and all infusions were begun within 10 minutes of MCA occlusion. Twenty-four hours after treatment, the rats underwent a careful neurological examination and were then sacrificed immediately. The size of areas of cerebral infarction was evaluated using 2,3,5-triphenyltetrazolium chloride staining techniques. The neurological grade of the rats correlated with the size of infarcted areas among all grades, irrespective of treatment (p less than 0.01). Neither naloxone nor TRH improved neurological function or reduced the size of infarction compared to saline-treated control rats. Treatment with TRH caused a significant increase in mean arterial blood pressure during infusion, but naloxone had no effect. These results suggest that neither TRH nor naloxone are effective in the treatment of acute focal cerebral ischemia.     

Neuroprotection by intrathecal application of liposome-entrapped fasudil in a rat model of ischemia

Pharmacological treatment for cerebral ischemia cannot attain sufficiently high concentrations of the drugs in the cerebrospinal fluid (CSF) without precipitating systemic side effects. The objective of this study is the development of a liposomal drug delivery system that maintains effective concentrations of protein kinase inhibitors fasudil in the CSF, resulting in neuroprotection against cerebral ischemia. Focal cerebral ischemia in rats was induced by middle cerebral artery occlusion using an intraluminal suture technique. Treated rats received 0.25 mg liposome-entrapped fasudil via the cisterna magna 2 hours after ischemic insult. Control rats received drug-free liposomes. Neurological condition and the infarct size were assessed at 24 and 72 hours after ischemia. The concentration of liposome-entrapped fasudil in the CSF was measured before sacrifice. Treated animals showed significantly improved neurological outcomes after the 24-hour observation period compared to the control group (p < 0.001). Treatment with 0.25 mg liposomal fasudil resulted in a reduction in the infarct area (24 hours: 29.0 +/- 4.4%, 72 hours: 28.1 +/- 3.9% of total brain slices) compared to controls (49.6 +/- 4.6%, p < 0.001), but there was no statistical difference between 24 and 72 hours. At 24 hours post-administration, CSF concentrations of liposome-entrapped fasudil were 45.4 +/- 31.5 micrograms/ml (20% of the injected dose). A single intrathecal injection of liposomal fasudil can maintain a therapeutic drug concentration in the CSF over a period of time, significantly decreasing infarct size in a rat model of acute ischemia.     

The therapeutic value of nimodipine in experimental focal cerebral ischemia. Neurological outcome and histopathological findings

Recent studies suggest that nimodipine, a potent calcium-channel antagonist that causes significant cerebrovascular dilatation, may improve neurological outcome after acute experimental permanent focal cerebral ischemia when given before or immediately after occlusion of the middle cerebral artery (MCA) in various animals. The authors describe the effect of nimodipine on cerebral ischemia in a rat model. At 1, 4, or 6 hours after occlusion of the MCA, rats were treated in a double-blind technique with either nimodipine, placebo, or saline. Neurological and neuropathological evaluation was performed at 24 hours. Neurological outcome was better in rats treated with nimodipine 1, 4, or 6 hours after occlusion (p less than 0.001, p less than 0.01, p less than 0.05 respectively), and the size of areas of infarction was statistically smaller in nimodipine-treated groups (p less than 0.01, p less than 0.01, p less than 0.05, respectively) when compared with control rats treated with saline or placebo. The best neurological outcome and the smallest area of infarction were found in nimodipine-treated rats 1 hour after occlusion. Compared with controls, the size of the periphery of the infarcted area was smaller in nimodipine-treated rats. The results show that nimodipine improves neurological outcome and decreases the size of infarction when administered up to 6 hours after ischemic insult. These results suggest a possible mechanism of action of nimodipine on the "penumbra" of the ischemic area.     

Effect of naloxone on cerebral perfusion and cardiac performance during experimental cerebral ischemia

Transient global cerebral ischemia (TGI) was induced in awake rats using the "four-vessel" occlusion model of Pulsinelli and Brierley. Blood pressure, arterial blood gases, cerebral blood flow, and cardiac output were measured during the acute (up to 2 hours) and chronic (2 to 72 hours) postischemic time periods. Coincident with the onset of TGI, cardiac output and caudate blood flow were depressed. The former returned to baseline within 30 minutes after the conclusion of TGI, and the latter progressed to hyperemia at 12 hours (81.8 +/- 4.9 vs 68.6 +/- 3.9 ml/min/100 gm tissue (mean +/- standard error of the mean] and oligemia at 72 hours (45.5 +/- 4.8 ml/min/100 gm tissue) post-TGI in the untreated control rats. Arterial blood gases and blood pressure were unchanged. Naloxone (1mg/kg) given at the time of TGI or as late as 60 minutes post-TGI and every 2 hours thereafter for 24 hours or bilateral cervical vagotomy prevented the depression in cardiac output and blocked the hyperemic-oligemic cerebral blood flow pattern that was predictive of stroke in this rat model. Changes in cardiac output after TGI in this model appear to be mediated by parasympathetic pathways to the heart from the brain stem. Opiate receptor blockade probably blocks endogenous opioid peptide stimulation of these brain-stem circulatory centers, which results in inhibition of parasympathetic activity and improvement in cardiac output. The usefulness of naloxone in the treatment of experimental stroke may be a function of its ability to improve cerebral perfusion in pressure-passive cerebrovascular territories. Variations in cardiac output during experimental stroke may explain the dissimilar responses to naloxone treatment reported by other investigators of experimental stroke.     

Hemodilution during cardiopulmonary bypass increases cerebral infarct volume after middle cerebral artery occlusion in rats

Although the optimal hematocrit during cardiopulmonary bypass (CPB) is not defined, excessive hemodilution may lead to organ ischemia via a reduction in oxygen-carrying capacity uncompensated by autoregulatory and/or rheologic increases in organ blood flow. As a result, the consequences of hemodilution in patients at risk for cerebral ischemia are not clearly understood. We designed this study to evaluate the effects of hemodilution in the setting of focal cerebral ischemia during CPB. Wistar rats surgically prepared for CPB were randomized to either hemodilution (hemoglobin (Hb), 6 g/dL; n = 9) or control (Hb, 11 g/dL; n = 8) groups and subsequently exposed to focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Immediately after the onset of MCAO (maintained for 90 min), 65 min of hypothermic (28 degrees C) CPB was initiated. Twenty-four hours later, functional neurological outcome and cerebral infarct volume were determined. Compared with controls, the hemodilution group had worse neurological performance (new score = 8 [2], hemodilution; versus 10 [2], control; P = 0.030) and larger total cerebral infarct volumes (182 +/- 84 mm(3), hemodilution; versus 103 +/- 58 mm(3), control; P = 0.043). In this experimental model of CPB with reversible MCAO-induced focal cerebral ischemia, hemodilution worsened neurological function and increased cerebral infarct volume.