利用激光散斑成像技术观察尤瑞克林对脑梗死大鼠脑血流的影响

目的 利用激光散斑成像技术研究尤瑞克林对大鼠脑梗死后局部脑血流的影响.方法 成年雄性SD大鼠24只,线栓法制备大鼠永久性大脑中动脉梗死模型.激光散斑成像系统观测缺血半球皮质及大脑中动脉供血区血流,2,3,5-三苯基氯化四氮唑(TTC)染色法测定脑梗死体积,并进行神经功能评分.结果 皮质及大脑中动脉供血区血流在大剂量组第1天及第2天给药后均有明显改善,部分大脑皮质血管增粗,血流速度加快,小剂量组及生理盐水组无明显变化,脑缺血48 h后,大、小剂量尤瑞克林组及生理盐水组的梗死体积分别为10.14%±3.02%,25.99%±3.90%,27.10%±3.32%,大剂量组与生理盐水组比较差异有统计学意义(F=61.14,P<0.01),小剂量组与生理盐水组比较差异无统计学意义.缺血后4 h,大剂量组神经功能损伤明显改善,小剂量组及生理盐水组无明显改变,36 h各组间的神经功能评分差异无统计学意义.结论 尤瑞克林可以减少大鼠局灶性脑缺血后梗死体积,延缓神经功能损伤,其作用可能与促进侧支循环的开放,增加大脑皮质和缺血区血流有关.     

尤瑞克林对糖尿病大鼠局灶性脑缺血再灌注后半胱氨酸天冬氨酸蛋白酶-12表达的影响

目的探讨尤瑞克林(urokallikrein)对糖尿病大鼠局灶性脑缺血再灌注损伤后半胱氨酸天冬氨酸蛋白酶-12(cysteinyl aspartate specific proteinase-12,caspase-12)表达的影响及其对糖尿病合并急性脑缺血再灌注损伤神经细胞的保护机制。方法将82只雄性SD大鼠随机分为假手术组(10只)、缺血组(36只)和尤瑞克林组(36只)。以无菌链脲佐菌素(STZ)腹腔注射制作糖尿病大鼠模型,采用Zea-Longa法制作大脑中动脉闭塞再灌注(MCAO/R)模型,比较各组大鼠脑缺血2h再灌注12、24、48h神经功能评分、缺血半暗带细胞凋亡数目及caspase-12表达的差异。结果与假手术组比较,缺血组和尤瑞克林组大鼠脑缺血再灌注12、24、48h神经功能评分、细胞凋亡数及caspase-12表达水平均升高(均P0.05),而尤瑞克林组神经功能评分、细胞凋亡数及caspase-12表达水平低于缺血组(均P0.05)。结论尤瑞克林对糖尿病大鼠局灶性脑缺血再灌注后神经细胞凋亡的抑制作用可能通过下调caspase-12表达而实现。     

尤瑞克林治疗急性期脑梗死老年患者应用CT灌注扫描临床分析

目的评价尤瑞克林治疗老年急性期脑梗死患者应用CT灌注扫描技术的临床效果。方法 2012-06-2014-06选取84例经头部CT或MRI确诊为急性期脑梗死的老年患者为研究对象,根据随机数字表将患者分为常规治疗组及尤瑞克林组各42例,常规治疗组口服阿司匹林,同时给予奥扎格雷钠静滴治疗,尤瑞克林组在常规治疗基础上静滴尤瑞克林,分别于治疗前后对2组患者行CTPI,观察2组患者治疗前后中心区及半暗带区脑灌注成像相对比值。对比2组患者治疗效果及治疗前后脑梗死面积及神经功能缺损评分(NIHSS)改善情况。结果尤瑞克林组总有效率为92.86%高于常规治疗组76.19%,差异有统计学意义(P0.05)。2组患者治疗后中心区及半暗带区中脑血容量(CBV)、脑血流量(CBF)、达峰时间(TTP)均高于治疗前(P0.05),且尤瑞克林组治疗后中心区及半暗带区中CBV、CBF、TTP均高于常规治疗组(P0.05)。尤瑞克林组治疗后梗死面积及NIHSS评分显著少于常规治疗组。结论通过CT灌注扫描可观察尤瑞克林对老年急性期脑梗死患者病灶中心区及半暗带区血流灌注的改善情况,对评价脑梗死患者预后具有重要的意义。     

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     

大鼠局灶性脑缺血模型缺血半暗带的定位研究

目的通过用组织病理学方法结合局部脑血流量(rCBF)测定,对大鼠局灶性脑缺血动物模型缺血半暗带的解剖定位进行初步探讨.方法用线栓法制成大鼠大脑中动脉(MCA)闭塞及再通模型、采用TTC染色法观察分组动物在MCA闭塞的不同时间再灌流48h后脑梗死灶的分布,并用氢清除法测定缺血区rCBF的变化.结果大鼠MCA闭塞1～2h,梗死灶主要位于缺血侧的外侧尾壳核和额顶叶皮质下部;MCA闭塞3h、梗死灶向周围扩大;MCA闭塞4h、梗死灶进一步扩展至大部分新皮质区,但与MCA闭塞6h时无明显区别.MCA闭塞后缺血侧的内侧尾壳核和额顶叶皮质上部rCBF下降至对照组的27%～45%.结论大鼠MCA闭塞后在2～3h的时间窗以内恢复血流,可使位于缺血边缘区的内侧尾壳核和额顶叶皮质上部脑组织被挽救,该区域可能相当于缺血半暗带的等值区.     

神经干细胞移植治疗大鼠脑缺血再灌注损伤实验研究

目的探讨大鼠胚胎神经干细胞移植治疗局灶性脑缺血再灌注损伤的可行性。方法孕龄8~10d的大鼠神经干细胞在体外扩增后,用免疫组织化学方法分别检测神经干细胞及其分化后代的特异性标志蛋白nestin、胶质纤维酸性蛋白(GFAP)和神经元特异性烯醇化酶(NSE)的表达。分别于缺血后不同时间窗将神经干细胞移植到局灶性脑缺血大鼠模型的缺血半暗带和梗塞中心,移植4w后比较不同移植部位神经干细胞存活、增殖和迁移的差异。结果从胎鼠中成功培养出悬浮生长的可表达nestin的神经球,其在含血清条件下可分化为表达GFAP的胶质细胞和表达NSE的神经元。神经干细胞移植4w后可见所有移植动物的细胞都存活,梗塞中心移植的细胞存活、增殖水平明显低于半暗带移植的细胞。结论大鼠胚胎神经干细胞移植到局灶性脑缺血再灌注损伤大鼠梗塞中心和半暗带均可长期存活,其增殖能力与移植部位密切相关。     

大鼠局灶性脑缺血β淀粉样前体蛋白mRNA在缺血半暗带的表达变化

目的 :研究大鼠局灶性脑缺血不同缺血时间皮质半暗带和中心区淀粉样前体蛋白 (APP)在转录水平表达规律。方法 :用线栓法建立大鼠局灶性脑缺血模型 ,剥取缺血半暗带及中心区皮质组织 ,采用半定量逆转录 聚合酶链式反应 (RT PCR) ,测定APPmRNA水平的变化。结果 :半暗带APPmRNA在缺血后 48h升高 ,缺血 72h达到高峰 ,缺血 1周后仍高于正常。缺血中心区APPmRNA在缺血后 72h和 96h高于正常水平。结论 :APPmRNA在缺血半暗带的表达上调 ,有可能加重缺血损伤。     

bFGF对大鼠局灶性脑缺血后神经细胞凋亡及Bcl-2、Bax的影响

目的探讨bFGF对缺血后神经细胞的保护作用。方法用线栓法制作局灶性脑缺血大鼠模型,于术前1h、术后第1天、第2天连续3天侧脑室注射bFGF,分1μg／d、2μg／d、4μg／d3组,观察缺血程度、梗塞体积、Bcl-2、Bax蛋白的合成。结果;bFGF能减轻脑缺血程度,减少梗塞体积(25．2％)及凋亡细胞数,提高半暗带内Bcl-2蛋白的合成,减低缺血灶内Bax蛋白的合成,各剂量组间无显著差异。结论bFGF可作为一种有效的神经细胞保护剂,保护神经细胞免受缺血的损害。     

大鼠局灶性脑缺血损伤中IGF-I mRNA表达

目的　观察局灶性脑缺血损伤中 IGF- I m RNA的表达特点 ,探讨其调控机制。方法　采用自体血凝块注入颈内动脉的方法制作大鼠局灶性脑缺血 2 h、4 h、6 h、12 h、2 4 h、4 8h模型 ,应用原位杂交及 RT- PCR方法 ,检测缺血中心区及半暗带区 IGF- I m RNA的表达。结果　局灶性脑缺血损伤时 ,缺血中心区及半暗带区 IGF- I m R-NA表达增加 ,尤以缺血半暗带区增加明显。结论　 IGF- I对局灶性脑缺血损伤具有保护作用。     

克林澳注射液对大鼠脑缺血后神经细胞凋亡及磷酸化Akt蛋白表达的影响

目的动态观察SD大鼠局灶性脑缺血再灌后神经细胞凋亡的变化及磷酸化Akt蛋白的表达并探讨克林澳注射液（简称克林澳）对其保护作用。方法用线栓法制备局灶性大脑中动脉缺血再灌注模型,以尼氏染色观察大鼠脑缺血再灌后皮质存活神经元,末端转移酶介导的缺口末端标记（TUNEL）方法检测神经细胞凋亡,免疫组化（SABC）方法检测磷酸化Akt蛋白表达。结果克林澳组再灌12h后各时间点半暗带区神经元较模型组多（P〈0.01）,TUNEL阳性细胞数显著减少（P〈0.01）,磷酸化Akt阳性细胞数明显增加（P〈0.01）。结论减少神经元凋亡,上调磷酸化Akt蛋白表达可能是克林澳保护脑缺血损伤的机制之一。     

Regional cerebral blood flow correlates of aphasia outcome in cerebral hemorrhage and cerebral infarction

The relationship between recovery from aphasia and regional cerebral blood flow (CBF) was compared in 87 patients, 44 with cerebral hemorrhage and 43 with non-embolic cerebral infarction. CBF values correlated poorly with aphasia outcome in patients with cerebral hemorrhage whereas a tight correlation was demonstrated in patients with non-embolic cerebral infarction. A marked variability of CBF values in the acute and subacute stage might account for the poor correlation between CBF and aphasia outcome in patients with cerebral hemorrhage. On the other hand, a sharp discrimination was achieved between those with a good recovery from aphasia and those with a poor recovery by the dimensions of the hematoma on CT. In non-embolic cerebral infarction, a relative frontal ischemia was associated with motor aphasia while a relative temporal ischemia was associated with sensory aphasia. This dichotomy was not demonstrated in the regional CBF values in patients with cerebral hemorrhage.     

Impaired dynamic cerebral autoregulation in middle cerebral artery stenosis

Abstract

Background and purpose: Analysis of dynamic cerebral autoregulation during transient falls in blood pressure is considered a sensitive and convenient method for evaluating patients with carotid artery stenosis. To this point, there have been few reports on the efficacy of using the thigh cuffs technique to analyse middle cerebral artery (MCA) stenosis. If it could be determined whether cerebral blood flow can be maintained (autoregulated) during sudden falls in arterial blood pressure (ABP), then it might be possible to identify patients with MCA stenosis who are at risk of stroke.

Methods: We used the thigh cuff technique to estimate dynamic cerebral autoregulation in 57 patients with MCA stenosis and 72 normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of the rise of MCA blood velocity and compared it with the rate of the rise of arterial blood pressure. In this manner, the dynamic cerbral autoregulation of 11 patients undergoing MCA M1 stent angioplasty was estimated both pre- and post-operation.

Results: The autoregulatory index (ARI) was significantly reduced in patients with stenosed/occluded MCA (3.24 ± 1.52), as compared with normal controls (5.25 ± 1.39; p<0.001) (results reported as mean ± SD). Poor ARI values are usually observed in patients with a higher degree of stenosis and particularly in patients with insufficient collateral compensation. ARI was significantly reduced in severe stroke patients (modified ranking scale≥1), as compared with asymptomatic or TIA patients (p<0.05). After MCA stent angioplasty was performed, there was a significant improvement in ARI in 11 subjects, which caused a mean increase in ARI from 2.08 ± 1.10 to 3.80 ± 1.36 (p=0.008).

Conclusions: Dynamic cerebral autoregulation is impaired in patients with middle cerebral artery stenosis. Assessing dynamic cerebral autoregulation may allow a subgroup of patients with MCA stenosis who are at risk of hemodynamic stroke to be identified. Dynamic cerebral disautoregulation in patients with severe MCA stenosis is mostly remedied by stent angioplasty.     

Impaired dynamic cerebral autoregulation in middle cerebral artery stenosis

BACKGROUND AND PURPOSE: Analysis of dynamic cerebral autoregulation during transient falls in blood pressure is considered a sensitive and convenient method for evaluating patients with carotid artery stenosis. To this point, there have been few reports on the efficacy of using the thigh cuffs technique to analyse middle cerebral artery (MCA) stenosis. If it could be determined whether cerebral blood flow can be maintained (autoregulated) during sudden falls in arterial blood pressure (ABP), then it might be possible to identify patients with MCA stenosis who are at risk of stroke. METHODS: We used the thigh cuff technique to estimate dynamic cerebral autoregulation in 57 patients with MCA stenosis and 72 normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of the rise of MCA blood velocity and compared it with the rate of the rise of arterial blood pressure. In this manner, the dynamic cerebral autoregulation of 11 patients undergoing MCA M1 stent angioplasty was estimated both pre- and post-operation. RESULTS: The autoregulatory index (ARI) was significantly reduced in patients with stenosed/occluded MCA (3.24 +/- 1.52), as compared with normal controls (5.25 +/- 1.39; p<0.001) (results reported as mean +/- SD). Poor ARI values are usually observed in patients with a higher degree of stenosis and particularly in patients with insufficient collateral compensation. ARI was significantly reduced in severe stroke patients (modified ranking scale>or=1), as compared with asymptomatic or TIA patients (p<0.05). After MCA stent angioplasty was performed, there was a significant improvement in ARI in 11 subjects, which caused a mean increase in ARI from 2.08 +/- 1.10 to 3.80 +/- 1.36 (p=0.008). CONCLUSIONS: Dynamic cerebral autoregulation is impaired in patients with middle cerebral artery stenosis. Assessing dynamic cerebral autoregulation may allow a subgroup of patients with MCA stenosis who are at risk of hemodynamic stroke to be identified. Dynamic cerebral disautoregulation in patients with severe MCA stenosis is mostly remedied by stent angioplasty.     

Sequential cerebral blood flow changes in short-term cerebral ischemia in gerbils

Using quantitative autoradiography, we studied sequential changes in regional cerebral blood flow during and after 2 minutes of bilateral common carotid artery occlusions in 18 gerbils. Occlusion (n = 4) led to severe ischemia in the forebrain (regional cerebral blood flow less than 5% of control [n = 4]) and midbrain (regional cerebral blood flow less than 10% of control), but was morphologically nonlethal. Reperfusion of the brain was complete, and regional cerebral blood flow was not different from control 1 minute after ischemia (n = 4), but hypoperfusion (regional cerebral blood flow 30-50% of control) occurred at 5 minutes (n = 3) and was pronounced at 1 hour (n = 4); at this stage blood flow was inhomogeneous. Hypoperfusion had disappeared at 4 hours (n = 3). Our results indicate that the well-documented sequence of cerebral blood flow changes (i.e., ischemia, initial recovery of blood flow, and delayed hypoperfusion) takes place even after nonlethal cerebral ischemia.     

Changes in cerebral glucose metabolism in newborn infants with cerebral infarction

Cerebral infarction in infants is not uncommon, and it differs in many important ways from cerebral infarction in older children and adults. Computed tomography, ultrasound, and conventional and diffusion-weighted magnetic resonance imaging are useful for diagnosing cerebral infarction, but these imaging techniques cannot be used to measure cerebral blood flow and metabolic activity. Abnormality in those parameters seems to follow a different pattern and time course than those in older patients. In this study, the rapid changes in regional cerebral blood flow and metabolic rate of glucose were estimated by single-photon emission computed tomography and positron emission tomography during the acute and subacute phases of neonatal infarction. Subacute increases in blood flow and metabolic rate in the infarcted area of a term infant with multiple apneic episodes within 2 days after birth were observed, as well as acute increases in both in the infarcted area of a term infant with acute clonic seizures within 24 hours after birth. Follow-up studies at 4 months for the first infant and at 10 days for the second infant demonstrated that both the blood flow and metabolic rate in the infarcted region decreased. The results of this study should contribute to an understanding of the relationship between blood flow and metabolic rate changes after neonatal infarction as well as to improvement of diagnosis of neurologic impairments in neonates.     

Liposome-entrapped superoxide dismutase reduces cerebral infarction in cerebral ischemia in rats

We studied the role of superoxide radicals in the pathogenesis of ischemic brain injury using a model of focal cerebral ischemia in 102 rats and liposome-entrapped CuZn-superoxide dismutase, which can penetrate the blood-brain barrier and cell membranes efficiently. The bolus intravenous administration of 25,000 units of liposome-entrapped CuZn-superoxide dismutase elevated superoxide dismutase activities in the blood and brain 1, 2, 8, and 24 hours later as well as in the ischemic hemisphere and contralateral cortex. Determined 24 hours after right middle cerebral and bilateral common carotid artery occlusion by the lack of staining for mitochondrial dehydrogenase activity with 2,3,5-triphenyltetrazolium chloride, infarct sizes were reduced by 33%, 25%, and 18% in the anterior, middle, and posterior brain slices, respectively, by treatment with liposome-entrapped CuZn-superoxide dismutase. Our data demonstrate that superoxide radicals are important determinants of infarct size following focal cerebral ischemia and that liposome-entrapped CuZn-superoxide dismutase may have pharmacologic value for the treatment of focal cerebral ischemic injury.