急性创伤性脑损伤动物模型早期局部脑血流量变化的实验研究

为了研究急性创伤性脑损伤早期局部脑血流量（ｒＣＢＦ）的变化，作者制作了闭合性机械脑损伤动物模型，采用氢清除法测定ｒＣＢＦ。结果显示脑损伤后早期ｒＣＢＦ即明显减少（Ｐ＜０．０５），伤后６～１２ｈ内下降最为明显，脑损伤的严重程度和ｒＣＢＦ下降程度呈显著正相关；皮质ｒＣＢＦ下降幅度大于白质。提示ｒＣＢＦ的变化反应了脑损伤的程度。作者认为ｒＣＢＦ降低是导致继发性脑损伤进行性加重的重要原因。     

鼠侧向液压脑损伤后脑血流量和葡萄糖利用率的改变

目的：探讨液压冲击脑损伤后脑血流量（ＣＢＦ），局部脑血流量（ｒＣＢＦ）与局部葡萄糖利用率（ｒＣＧＵ）的变化及其对神经元继发性损伤的影响。方法：应用激光多普勒流量计和定量放射自显影技术。结果：液压冲击脑损伤导致６０秒内ＣＢＦ短暂升高然后显著下降，且持续６０分钟低于正常，同侧和对侧大脑半球的ＣＢＦ相应降为正常值的７９％和９３％。外伤后１小时，损伤侧脑皮层，丘脑及海马的ｒＣＢＦ下降１２％～５９％，对侧大脑半球相应区域则下降１０％～４０％。相反，ｒＣＧＵ在冲击区周围脑皮质及同侧丘脑和海马区升高２７％～１０１％，在对侧大脑半球相应区域则升高２０％～９１％，海马区由液压冲击引起的ｒＣＢＦ和ｒＣＧＵ分离性变化十分显著，同侧海马ＣＡ１和ＣＡ２－３区存活的神经元数量在损伤后两星期时显著减少。结论：ｒＣＢＦ和ｒＣＧＵ的分离性变化是引起外伤后神经元尤其是海马区神经元继发损伤的主要因素。     

^133Xe吸入法测定震颤麻痹脑局部区域血流量

用＾１３３Ｘｅ吸入法测定２０例震颤麻痹及１０名正常人脑局部区域血流量（ｒＣＢＦ），病例组双半球、脑干－小脑ｒＣＢＦ均明显低于正常健康组，病例组ｒＣＢＦ值与病情程度无关，ＣＴ示弥漫性皮质萎缩、皮质下萎缩及混合性萎缩，其ｒＣＢＦ明显低于ＣＴＡ正常者，病例组脑动脉对ＣＯ２扩张反应能力差。     

脑血管病性痴呆与Alzheimer病患者脑局部区域的血流量

目的 测定多灶脑梗塞痴呆及Ａｌｚｈｅｉｍｉｅｒ病患者的脑局部区域的血流量（ｒＣＢＦ），方法 用＾１３３氙（＾１３３Ｘｅ）吸入法测定１０例多灶脑梗塞痴呆患者。１０例Ａｌｚｈｅｉｍｅｒ病及２０名正常人的ｒＣＢＦ。结果 两个病例组双半球，脑干－小脑ｒＣＢＦ均明显低于正常健康组，脑梗塞痴呆组多数病例双侧半球灰质ｒＣＢＦ降低呈斑块状，Ａｌｚｈｅｉｍｅｒ病例组均为双侧大脑半球弥散性对称性的ｒＣＢＦ降低，前乾脑     

光化学诱导鼠大脑中动脉闭塞及再通模型

应用光化冷光源仪（金属卤化物灯）诱导鼠大脑中动脉（ＭＣＡ）闭塞，并于光照血管局部滴注尼莫地平致闭塞血管再通。结果发现：光照３０ｍｉｎ后鼠脑皮质及基底节局部脑组织血流量（ｒＣＢＦ）明显下降，且维持９０ｍｉｎ以上。同时，光照侧脑组织含水量明显增加。尼莫地平局部滴注２０ｍｉｎ后皮质ｒＣＢＦ则有所回升，用药后３０ｍｉｎｒＣＢＦ明显上升，为缺血前ｒＣＢＦ的１３１．１％。组织病理形态观察显示：光照例鼠ＭＣＡ及其周围毛细血管管腔内均有明显血栓形成，缺血１２ｈ梗塞区神经元、线粒体及内质同明显肿胀，神经元坏死。再灌注后病理损害更为明显。实验鼠先照例额、顶叶皮质及新纹状体出现边界清晰、范围较恒定的苍白梗塞灶。该模型的建立为进一步研究脑缺血及脑梗塞提供了新的工具。     

自发性脑出血后神经功能与脑血流动态变化的相关研究

研究６６例自发性脑出血（ＳＩＣＨ）患者急性期、亚急性期、恢复期的ＳＰＥＣＴ脑血流显像和神经功能的关系，发现：（１）临床神经功能与ｒＣＢＦ的变化密切相关；（２）失语组与无失语组者Ｂｒｏｃａ区和Ｗｅｒｎｉｃｋｅ区ｒＣＢＦ亦存在显著差异，失语的恢复与ｒＣＢＦ的恢复相一致；（３）交叉性小脑失联络（ＣＤＤ）现象与出血量及出血部位有关，出血量大和／或优势半球出血易引起ＣＤＤ。提示积极改善脑出血患者亚急性期和恢复期的脑血流量，有助于临床神经功能的恢复。     

脑出血患者血浆及脑脊液内皮素－1含量对照研究

本文对照研究了脑出血患者血浆及脑脊液（ＣＳＦ）内皮素－１（ＥＴ－１）含量改变及其临床意义。发现脑出血患者血浆与ＣＳＦ、ＥＴ－１含量均增高；单纯脑血肿者以血浆含量增高为主；脑实质出血伴有脑室系统或蛛网膜下腔出血（ＳＡＨ）者血浆及ＣＳＦ含量均显著升高；小量出血与中大量出血比较血浆含量无显著性，而大量出血者ＣＳＦ、ＥＴ－１含量增高。提示脑出血者血浆ＥＴ－１增高可能与机体应激有关，而ＣＳＦ、ＥＴ－１升高可能与血脑屏障（ＢＢＢ）被破坏及损害或刺激室周组织、下丘脑、脉络丛脑膜，引起分泌释放增加有关。ＣＳＦ、ＥＴ－１增高者应警惕迟发性脑血管痉挛。     

长时间电针时大鼠脑内八肽胆囊收缩素的生成和释放加速

本文用大鼠进行实验，观察了长时间电针刺激时脑脊液中和中脑层水周围灰质内ＣＣＲ－８样免疫活性物质（ＣＣＫ－８－ｉｒ）含量，并用Ｎｏｒｔｈｅｒｎ印迹法测定脑内ＣＣＫｍＲＮＡ含量的变化，结果表明，电针１ｈ后大鼠脑脊液中ＣＣＫ－８－ｉｒ的浓度增高，２ｈ后中脑导水管周围灰质的含量也明显升高，８ｈ后大鼠脑内ＣＣＫ－８ｍＲＮＡ含量显著增加，表明长时间电针加速脑内ＣＣＫ－８的生成和释放，最终加速了ＣＣＫ基因表达，     

缺血性脑中风患者高压氧治疗价值及机理探讨

目的　了解高压氧治疗缺血性脑中风的治疗价值及机理。方法　对 ４７ 例急性缺血性中风患者用高压氧（ Ｈ Ｂ Ｏ）治疗前后测定 ｒ Ｃ Ｂ Ｆ及检查脑电图的变化。结果　治疗后 Ｈ Ｂ Ｏ 组患者 ｒ Ｃ Ｂ Ｆ 值均较治疗前明显降低（灰质重于白质，病灶侧重于非病灶侧）；而对照组患者 ｒ Ｃ Ｂ Ｆ值较治疗前明显增加（ Ｐ＜ ０．０５）。治疗后 Ｈ Ｂ Ｏ 组 Ｅ Ｅ Ｇ 频率虽较治疗前增快，慢波减少，但无统计学意义；而对照组 α指数，波频改善显著，慢波明显减少（ Ｐ＜ ０．０５）。结论　 Ｈ Ｂ Ｏ 治疗不仅可使正常脑组织血管收缩，脑血流量减少，而对缺血性损害侧大脑半球的血管收缩更为显著，有加重“脑盗血”发生、发展的趋势。     

抑郁症患者的脑单光子发射计算机断层摄影研究

为观察抑郁症患者局部脑血流（ｒＣＢＦ）情况，对１１例处于症状发作期的抑郁症患者及１３名正常对照者用９９ｍＴｃ标记的亚锡双半胱乙脂进行脑单光子发射电子计算机断层摄影（ＳＰＥＣＴ）。结果显示，观察组与对照组比较，左下额、左前颞及扣带皮质的ｒＣＢＦ显著下降（Ｐ＜０．０１），而右上额、右下额和两侧顶叶、枕叶的ｒＣＢＦ也有下降（Ｐ＜０．０５）。观察组尚存在上额皮质ｒＣＢＦ两侧非对称性（Ｐ＜０．０５），而对照组未见相应的非对称性。提示抑郁症发作时存在某些脑功能区ｒＣＢＦ下降以及两侧脑功能区局部的ｒＣＢＦ不对称性。     

Dynamic single-section CT demonstrates reduced cerebral blood flow in acute intracerebral hemorrhage

Optimum blood pressure (BP) management in acute intracerebral hemorrhage (ICH) remains controversial. BP reduction may limit hematoma expansion, but may also exacerbate ischemia. Reduced regional cerebral blood flow (rCBF) has been reported in ICH. Its extent and precise pattern, however, remain uncertain. Dynamic single-section CT perfusion (CTP) is rapid, easily performed and offers superior spatial resolution to PET, SPECT and MRI. It may be the most applicable method for assessing the effects of BP management on rCBF in ICH. We sought to assess whether CTP can identify rCBF abnormalities in acute ICH in 5 patients with ICH who underwent CTP within 24 h of symptom onset. rCBF was measured in serially expanded 2-mm rings around the hematoma and compared with rCBF in the uninvolved hemisphere. Mean time to CTP was 9 h (range 3-23). Mean ICH volume was 25 ml (range 9-64). Perihematoma perfusion was reduced in all patients compared with contralateral hemisphere rCBF. rCBF reduction was most pronounced immediately adjacent to the hematoma (p < 0.05 at 2 mm, p = 0.084 at 4 mm, p > 0.2 at 6 and 8 mm). Perihematoma rCBF increased as a function of the distance from hematoma perimeter. Rate of rCBF increase over distance correlated with time from onset (p = 0.006). We conclude that CTP identifies a rim of reduced rCBF in ICH. A gradient of hypoperfusion appears to extend at least 4 mm beyond the hematoma edge and may be time dependent. Whether reduced CBF is associated with perihematoma ischemia requires additional study.     

Transtentorial diaschisis: reduction of cerebellar blood flow caused by supratentorial local cerebral ischemia in the gerbil

To assess the effect of supratentorial cerebral ischemia on infratentorial brain function, changes in regional cerebellar blood flow (rCeBF), after right carotid occlusion for 4 hours, were studied in 30 mongolian gerbils. The regional cerebral blood flow (rCBF) in the occluded cerebral hemisphere and rCeBF in both cerebellar hemispheres were measured simultaneously by hydrogen clearance methods. Before carotid occlusion, rCBF was 0.44 +/- 0.07 ml/g brain/min, and rCeBF in the left and right cerebellar hemispheres was 0.37 +/- 0.09 and 0.40 +/- 0.09 ml/g brain/min, respectively. After carotid occlusion, rCBF decreased in all animals showing levels of above 0.20 ml/g brain/min in 14 (group A), between 0.10 and 0.19 ml/g brain/min in 7 (group B) and below 0.10 ml/g brain/min in 9 (group C). rCeBF exhibited no changes in group A and a mild reduction in group B after carotid occlusion. In group C, rCeBF was significantly reduced 30 min after carotid occlusion in the left cerebellar hemisphere followed subsequently by bilateral reduction. In groups B and C, supratentorial brain edema was observed 4 hours after occlusion, but the degree of edema was moderate. The results of the present study suggest that depression of infratentorial brain function may occur after supratentorial local cerebral ischemia, presumably due to diaschisis.     

脑出血大鼠局部脑血流量的改变及尼莫地平的干预作用

目的 探讨脑出血(ICH)后脑组织局部脑血流量(rCBF)的改变及尼莫地平的干预作用.方法 SD大鼠72只随机分成ICH组、尼莫地平组和正常对照组,采用Nath 改良法建立ICH模型,尼莫地平组大鼠腹腔注射尼莫地平1 mg/kg,对照组注射等量生理盐水,在大鼠ICH后1 h、4 h、24 h、48 h用氢清除法测定其rCBF并与正常大鼠比较.结果 ICH组出血后1 h、48 h组出血侧皮质、基底节区rCBF较正常对照组明显下降(均P<0.05); 不同时间点尼莫地平组出血侧皮质、基底节区rCBF显著高于ICH组(均P<0.05).ICH组出血后4 h、24 h rCBF有回升,与正常对照组差异无统计学意义.尼莫地平组出血后各时间点出血侧皮质、基底节区rCBF与正常对照组差异无统计学意义.结论 ICH后有明显rCBF降低,尼莫地平能干预此改变.     

Inducible cyclooxygenase-2 expression after experimental intracerebral hemorrhage

Cyclooxygenase-2 (COX-2) is an inducible isoform of cyclooxygenase, which catalyzes the conversion of arachidonic acid to prostaglandins and thromboxane. Recent evidence suggests it has a pathological role in cerebral insults, but its involvement in intracerebral hemorrhage (ICH) is unknown. The present study investigates the temporal and anatomic distribution of COX-2 as well as the effect of the selective COX-2 inhibitor NS-398 on brain edema formation and cerebral blood flow in a rat model of ICH. Immunohistochemistry for COX-2 was performed in control rats and 6 h, as well as 1, 3, 7 and 10 days after the injection of 100 microl autologous blood into the right basal ganglia. Double-labeling immunohistochemistry was used to determine the type of COX-2 immunoreactive microvascular-associated cells. Western blot analysis was used to quantify COX-2 protein. The effect of NS-398 on brain water content, ion concentration and cerebral blood flow were assessed 24 h after ICH. The results demonstrated that COX-2 protein was expressed in control brain tissue and induced significantly in the ipsilateral hemisphere at 6 h, as well as 1 and 3 days after ICH. Increased staining of COX-2 in neurons was observed around the blood clot with a peak at 6 h. COX-2 was induced in endothelial cells, perivascular cells as well as infiltrating leukocytes 1 day after ICH. Brain water and ion contents and cerebral blood flow were unaffected by NS-398 administration. Thus, although COX-2 expression was increased in the ipsilateral hemisphere after an autologous blood injection, its products do not appear to be major regulators of blood flow or edema formation following ICH.     

Cerebral microembolization in the rat: Changes in blood-brain barrier permeability and cerebral blood flow as related to the degree of ischemia

Unilateral cerebral microembolism was performed in the rat by injecting calibrated, 50 micrometers in diameter, carbonized microspheres into the internal carotid artery. The events that follow brain ischemia due to cerebral embolization were studied by the analysis of the blood-brain barrier (BBB) function, the degree of regional cerebral blood flow (CBF) and the development of brain edema. Two hours after embolization there was no change in the brain water content. The local CBF (14C-ethanol technique) was only reduced in the ipsilateral hemisphere. Twenty-four hours after embolization the brain water content was increased significantly in the ipsilateral, but not in the contralateral hemisphere. Local CBF further decreased in the ipsilateral hemisphere and a reduction in flow was also observed in the contralateral hemisphere. Embolization led to an increase in the BBB permeability, analysed as regional penetrability of 3H-dextran and of Evans blue-albumin complexes, which was restricted to the side of the injection of the microspheres.     

Changes in regional cerebral blood flow during the course of classic migraine attacks

Regional cerebral blood flow (rCBF) following carotid arteriography was studied in thirteen patients with classic migraine. Using the 133xenon intraarterial injection method, rCBF was measured in 254 areas in one hemisphere. Nine patients developed a characteristic attack following arteriography and were examined by a series of rCBF studies, spaced by intervals of 5 to 10 minutes. A wave of reduced blood flow originating in the posterior part of the brain and progressing anteriorly was observed in eight of the nine patients. The oligemia advanced at a speed of 2 mm per minute over the hemisphere, progressing anteriorly but not crossing the rolandic or sylvian sulcus. Typically, the spreading oligemia reached the primary sensorimotor area after symptoms from that area had begun and persisted there long after the focal symptoms had disappeared. The observed time course suggests that the focal symptoms are not secondary to the oligemia. We suggest that focal symptoms and blood flow changes may be secondary to spreading depression of Leao.     

尼莫地平减轻蛛网膜下腔出血后脑损伤

目的 探讨尼莫地平对蛛网膜下腔出血(SAH)后脑损伤的防治作用。方法 用血管内穿刺法制作大鼠SAH模型。对SAH组和尼莫地平处理组观察24h内局部脑血流量(rCBF)和脑组织水、电解质含量的动态变化。结果 SAH后rCBF迅速降低，1h达最低值，24h内持续于低水平状态。SAH后6h、24h脑组织含水率和Na^ 含量明显增加，K^ 含量减低；脑组织Ca^2 含量在SAH后1h开始显著增加。尼莫地平对上述的指标均有改善作用。结论 尼莫地平可减轻实验性SAH后脑损伤。     

大鼠实验性脑出血后脑组织中c-fos基因的表达与局部脑血流的改变

目的 探讨大鼠实验性脑出血后脑组织中即刻早期基因c-fos的表达和局部脑血流的变化。方法 采用Nath改良法建立大鼠脑出血模型；免疫组化法及RT－PCR法测定其脑组织中fos蛋白和c-fos mRNA的表达；氢清除法测定其局部脑血流。结果 大鼠血肿周围区（基底节）在脑出血后1小时即出现fos蛋白的表达，至3小时达高峰；c-fos mRNA于出血后1小时达表达高峰,至3小时后仍有较高水平的表达；出血后1小时全脑的的血流量均下降，4小时恢复至对照组水平，并维持至出血后24小时，随着的24小时内再次出现脑血流下降。结论 大鼠脑出血后，血肿周围区和双侧皮质区的脑组织中存在着c-fos基因的快速而长久的诱导表达。局部脑血流的下降相对短暂，且脑血流的下降在时程上与c-fos基因的表达不相一致。     

Alterations in regional cerebral blood flow following brain injury in the rat

To elucidate the temporal changes in regional cerebral blood flow (rCBF) after experimental traumatic brain injury, serial rCBF measurements were made during a 24-h period following fluid-percussion (F-P) traumatic brain injury in the rat. Brain injury of 2.2 atm was induced over the left parietal cortex and serial measurements of rCBF were performed using the radiolabeled microsphere method. rCBF values were obtained prior to injury and at 15 and 30 min and 1, 2, 4, and 24 h postinjury. At 15 min postinjury, there was a profound, wide-spread reduction in rCBF in all brain regions studied (p less than 0.05). At 30 min and 1 h postinjury, all brain regions except pons-medulla and cerebellum showed significantly reduced rCBF compared to the preinjury values (p less than 0.05). By 2 h postinjury, however, a significant focal reduction of rCBF was observed only in the cerebral tissue surrounding the trauma site (p less than 0.05); rCBF in the remaining brain regions had recovered to the preinjury levels. By 4 h postinjury, rCBF had returned to normal in all brain regions studied. This recovery of rCBF was still evident at 24 h postinjury. The present study demonstrates that, following the experimental traumatic brain injury in the rat, (a) an initial global suppression of rCBF occurs up to 1 h postinjury; (b) at the trauma site, a more persistent focal reduction of rCBF occurs; and (c) these alterations in rCBF after trauma dissolve by 4 h postinjury.(ABSTRACT TRUNCATED AT 250 WORDS)     

经腹腔应用阿加曲班对脑出血后凝血酶神经毒性的抑制作用

目的:探讨经腹腔应用阿加曲班治疗脑出血（ICH）后凝血酶神经毒性损伤的可能性。方法:①研究阿加曲班对ICH及凝血酶注入后脑水肿、细胞损伤的影响。Wistar大鼠60只,随机分为假手术对照组（只进针不注血）;ICH组（50μL自体尾血注入右尾状核）;ICH+阿加曲班干预组(50μL自体尾血注入大鼠右侧尾状核,分别于术后3和12h经腹腔给予阿加曲班0.9mg·kg^-1,总量0.6mL);凝血酶组(10U·2μL^-1凝血酶注入大鼠右侧尾状核);凝血酶+阿加曲班干预组(10U·2μL^-1凝血酶注入大鼠右侧尾状核,分别于术后3和12h经腹腔给予阿加曲班0.9mg·kg^-1,总量为0.6mL)。各组均n=12,术后24h处死各组大鼠,每组中6只用于检测脑组织水含量,6只检测caspase-3免疫反应细胞及TUNEL阳性细胞数。②经腹腔注射阿加曲班对血肿容积的影响:建立胶原酶ICH大鼠模型组:注入Ⅰ型胶原酶+肝素;阿加曲班组:胶原酶ICH模型成功后3及12h分别经腹腔注入阿加曲班溶液0.9mg·kg^-1,每次注入液体量为0.6mL,测定两组大鼠脑组织血肿血红蛋白的含量(测定血红蛋白A₅₅₀值)以评价阿加曲班对血肿容量的影响。结果:自体血ICH及凝血酶模型大鼠在阿加曲班干预后,ICH组及凝血酶组的TUNEL阳性细胞数、caspase-3阳性细胞数明显下降（P<0.01或P<0.05）,脑组织水肿含量百分比明显降低（P<0.05）。胶原酶ICH血红蛋白A值为（0.45±0.12）,阿加曲班干预组为（0.46±0.09）,差异无统计学意义（P>0.05）。结论:ICH后3～12h经腹腔注入阿加曲班可减轻ICH后的脑水肿及细胞凋亡性损伤,且没有血肿增大的不良反应。