猪蛛网膜下腔出血后脑血管痉挛模型

目的建立猪SAH模型并研究其脑皿流灌注的变化。方法实验猪随机分为SAH组（n=5）和假手术组（n=4）。SAH组在右额颞开颅向鞍上池内注入自体动脉血制成SAH模型,假手术组注入等量生理盐水。4d后行SPECT—CT同机融合扫描并以大脑小脑比（corticocerebellar ratio,CCR）、相对离散度（relative dispersion,RD）半定量描述大脑半球血流量和血流分布离散度。7d后对海马行苏木精-伊红染色,观察神经元形态变化。结果CT证实血液积聚于鞍上池,造模成功。SAH组左右侧CCR（1．768±0．298,1,382±0．192）均较假手术组对应侧（2．131±0．246,1．988±0．346）显著下降（P〈0．05）;SAH组两侧CCR差异亦有统计学意义（P〈0．05）。SAH组右侧RD（0．417±0．015）较假手术组右侧（0．389±0．015）显著增加（P〈0．05）,SAH组左侧RD（0．406±0．023）与假手术组左侧（0．378±0．030）差异无统计学意义（P〉0．05）,SAH组两侧RD差异无统计学意义（P〉0．05）。苏木精-伊红染色证实SAH组海马神经元形态异常。结论猪SAH模型符合SAH血管痉挛引起的异常脑血流灌注特征,为此类疾病研究提供了理想的大型动物模型。     

尼莫地平预防创伤性蛛网膜下腔出血所致的脑血管痉挛

本文观察尼莫地平预防创伤性蛛网膜下腔出血(SAH)所致的脑血管痉挛(CVS)。将创伤性SAH病人136例分为两组,尼莫地平组(65例)于伤后24小时内给予尼莫地平治疗,对照组(71例)采用一般综合治疗各三周。结果提示尼莫地平组死亡率(24.6％)、CVS发生率(26.1％)分别低于对照组(33.8％和36.6％),说明尼莫地平预防创伤性SAH所致的CVS有效。     

海马硬化致颞叶癫癎的SPECT与MRI研究

目的探讨SPECT脑血流灌注显像结合MRI测量海马体积对海马硬化致颞叶癫癎患者致灶的定位价值。方法采用99Tcm-双半胱乙酯(99Tcm-ECD)SPECT脑血流灌注显像对双侧海马血流灌注进行定性和半定量分析,MRI测量双侧海马体积,分析海马硬化致颞叶癫癎(颞叶癫癎组)患者患侧海马相对脑血流量与相应区域海马体积的相关性。结果颞叶癫癎组患者患侧海马相对脑血流量[(46.04±7.94)ml/(100 g·min)]低于对侧[(54.76±9.62)ml/(100 g·min);t=-2.966,P=0.005]和正常对照者[(64.87±7.28)ml/(100 g·min);t=-4.824,P=0.000],且海马体积[(1.69±0.39)cm3]小于对侧[(2.68±0.41)cm3;t=-7.410,P=0.000]和正常对照者[(3.50±0.39)cm3;t=-16.340,P=0.000]。海马硬化致颞叶癫癎患者患侧海马相对脑血流量与相应区域海马体积呈正相关(r=0.394,P=0.017)。结论海马硬化致颞叶癫癎患者患侧海马相对脑血流量降低、海马体积缩小,二者呈正相关。SPECT脑血流灌注显像结合MRI测量海马体积,可以作为致灶切除术前准确定位的参考依据。     

氢化泼尼松对蛛网膜下腔出血患者脑灌注的影响

目的探讨大剂量氢化泼尼松对蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)患者脑灌注的影响。方法将19例CT分级在Ⅲ级以下的SAH患者随机分成2组:①治疗组,大剂量氢化泼尼松(1.0mg/kg)冲击治疗。②对照组,单纯应用一般治疗。氢化泼尼松冲击治疗3天后,行脑CT灌注成像扫描,监测颞叶及额叶脑血管灌注情况,结合临床症状判断脑血管痉挛的程度。结果9例应用大剂量氢化泼尼松加上一般治疗的患者,与单纯一般治疗组相比,临床症状及额叶、颞叶的脑血流情况均得到明显改善。脑血容量(CBV),脑血流量(CBF),平均通过时间(MTT),较对照组有明显提高(P(0.05)。结论大剂量氢化泼尼松冲击治疗能够提高蛛网膜下腔出血患者的脑灌注,从而减轻脑血管痉挛,改善脑供血。     

R-型钙通道阻滞剂对自发性蛛网膜下隙出血脑血流量的作用

目的：研究R-型钙通道阻滞剂SNX-482对大鼠自发性蛛网膜下隙出血（SAH）脑血流量减少的改善作用,并与L-型钙通道阻滞剂尼莫地平进行比较。方法：建立大鼠鞍上池SAH模型,分为SAH组、SAH＋尼莫地平组、SAH＋SNX-482组和假手术组。SAH＋尼莫地平组和SAH＋SNX-482组分别于模型建立后第1、2天向脑池内注射尼莫地平5峙或SNX-4825μg,第3天行神经功能评分、荧光微球法测定脑血流量以及脑组织大体病理观察。结果：SAH大鼠模型,据Sugawara大鼠SAH病理分级为中度。3组间神经功能评分差异无统计学意义（P〉0．05）;尼莫地平对脑血流量下降无明显治疗作用（P〉0．05）;SNX-482可减少SAH引起的脑血流量下降（P〈O．05）。结论：R-型钙通道阻滞剂很可能成为有效的SAH脑血管痉挛治疗药物。     

应用单光子发射计算机断层扫描脑血流灌注显像评价颈内动脉球囊闭塞试验后大脑耐受性

目的 评估单光子发射计算机断层扫描(SPECT)脑血流灌注显像在球囊闭塞试验(BOT)中的评价效用.方法 31例颈内动脉瘤患者接受了暂时性BOT.在闭塞球囊排空前5min,大约740MBq锝标双半胱乙脂(99mTc-ECD)由静脉注入,随后进行单光子发射计算机断层扫描.所得图像进行视觉分析、分级(正常、轻度、中度和重度灌注减低)并计算患侧/健侧(L/N)感兴趣区内放射性计数比值.结果 SPECT提示了24例受试者在暂时性球囊闭塞后出现了异常灌注,而只有4例出现了神经症状.正常血流灌注组L/N比值范围为0.98±0.03(7例),轻度血流灌注减低组L/N比值范围为0.89±0.03(11例),中度血流灌注减低组L/N比值范围为0.81±0.03(7例),重度血流灌注减低组L/N比值范围为0.66±0.04(6例),各组间的差异有统计学意义(P=0.000).结论 BOT联合负荷SPECT评价颈内动脉闭塞后的大脑耐受性是一种易行、客观、敏感的方法,所得初步结果需更多病人数量来证实.     

尼莫地平负荷SPECT脑血流灌注显像在急性非致残性脑血管病中的诊断价值

目的分析尼莫地平负荷脑血流灌注显像在急性非致残性脑血管病中的诊断价值。方法选取2017-01-01-2017-11-01在厦门大学附属第一医院就诊的35例急性非致残性脑血管病患者,行MRI、99Tcm-ECD静息及尼莫地平负荷SPECT脑血流灌注显像。分别在双侧额叶、颞叶、顶叶、枕叶、基底节区、小脑、脑干对称部位勾画感兴趣区(regions of interests,ROI),并记录各个ROI平均放射性计数,分析负荷前后SPECT图像及局部脑血流量(regional cerebral blood flow,rCBF),观察负荷前后脑血流灌注的变化情况,比较MRI、静息及尼莫地平负荷SPECT脑血流灌注显像对急性非致残性脑血管病责任病灶诊断阳性率的差异。采用卡方检验分析数据。结果在急性非致残性脑血管病中,MRI、静息及尼莫地平负荷SPECT脑血流灌注显像诊断阳性率分别为45.7%(16/35)、71.4%(25/35)、91.4%(32/35)。负荷前后rCBF变化的4种类型情况:A型:静息显像rCBF正常,负荷后rCBF减低5个;B型:静息rCBF减少,负荷后rCBF降低无明显改善11个;C型:静息rCBF减少,负荷后rCBF降低更明显8个;D型:静息时rCBF降低,负荷后rCBF改善11个。结论联合尼莫地平负荷前后SPECT脑血流灌注显像可明显提高急性非致残性脑血管病病灶诊断阳性率,且能够有效评估脑血管储备功能。     

金纳多治疗慢性脑供血不全的临床研究

目的探讨银杏叶提取物一金纳多治疗脑梗塞的疗效和SPECT脑血流灌注显像对慢性脑功能不全患者的诊断价值。方法对52例眩晕患者和20例正常对照者进行SPECT脑血流灌注显像检查,用金纳多20ml治疗疗程一周,金纳多片1片一日三次共30天,治疗前后进行疗效评价和SPECT脑血流灌注显像检查。结果52例患者全部出现脑血流量下降,多数分布在左颞,额叶;40%患者的脑缺血程度与健侧相比下降20%以上.60%患者脑血流量减少程度低于20%,39例患者表现为大脑两侧之血流量减低。金纳多治疗后脑血流量灌注显像结果显示大部分脑血流低灌注区恢复或不同程度改善。临床症状消失。全部患者脑CT/MRI及TCD检查均正常。结论金纳多对慢性脑供血不全治疗是十分安全有效的药物,SPECT脑血流量灌注显像有助于眩晕患者的病因学诊断,和治疗效果的评价。     

经颅多普勒对蛛网膜下腔出血导致血管痉挛的临床研究

目的研究实时床旁经颅多普勒(transcranial doppler,TCD)在蛛网膜下腔出血(subarachnoid hemorrhage,SAH)中对脑血管痉挛(cerebral vasospasm,CVS)的预警和治疗指导作用。方法采用前瞻性研究TCD实时监测180例CT确诊SAH患者大脑中动脉(middle cerebral artery,MCA)的动脉平均峰值流速(mean blood velocity,Vm)、搏动指数(pulsatility index,PI)、阻力指数(resistance index,RI)和血流频谱,自身健侧作为正常对照,对符合CVS诊断标准的使用尼莫地平进行治疗,观察疗效。结果与健侧相比,出血侧PI、RI增大,Vd、Vm减小,其中以Vd减小较明显,与健侧相比有显著差异意义(P0.01),Vs与健侧相比无显著差异(P0.05);CVS组与非CVS组相比Vm明显增加,差异有统计学意义(P0.001)。监测SAH后出现血管痉挛52例(28.89%),经尼莫地平治疗均获得缓解。结论采用TCD监测SAH患者脑血流变化,其对血流的监测为临床诊断和个性化治疗SAH后CVS提供参考依据,经TCD的预警和干预明显提高了SAH的疗效。     

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。     

尼莫地平加脑脊液置换对蛛网膜下腔出血脑血管痉挛的疗效观察

目的探讨尼莫地平或罂粟碱静脉输注加脑脊液置换治疗自发性蛛网膜下腔出血（SAH）脑血管痉挛的效果。方法以HUNT-HESS分级系统对SAH分级,单用尼莫地平持续泵入或罂粟碱静脉输注治疗19例,在上述治疗的基础上同时脑脊液置换治疗30例,观察指标为临床表现及影像学所见,如DSA、CT及脑电图。结果单用尼莫地平或罂粟碱治疗的19例病人,与采用尼莫地平或罂粟碱加脑脊液置换治疗的效果比较,差异有统计学意义,后者优于前者。结论尼莫地平或罂粟碱静脉输注加用脑脊液置换是治疗SAH后脑血管痉挛的有效方法。     

A Site-Specific,Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage

Nimodipine is the only drug approved for use by the Food and Drug Administration for improving outcome after aneurysmal subarachnoid hemorrhage (SAH). It has less than optimal efficacy, causes dose-limiting hypotension in a substantial proportion of patients, and is administered enterally 6 times daily. We describe development of site-specific, sustained-release nimodipine microparticles that can be delivered once directly into the subarachnoid space or cerebral ventricles for potential improvement in outcome of patients with aneurysmal SAH. Eight injectable microparticle formulations of nimodipine in poly(DL-lactide-co-glycolide) (PLGA) polymers of varying composition were tested in vitro, and 1 was advanced into preclinical studies and clinical application. Intracisternal or intraventricular injection of nimodipine–PLGA microparticles in rats and beagles demonstrated dose-dependent, sustained concentrations of nimodipine in plasma and cerebrospinal fluid for up to 29 days with minimal toxicity in the brain or systemic tissues at doses <2 mg in rats and 51 mg in beagles, which would be equivalent of up to 612–1200 mg in humans, based on scaling relative to cerebrospinal fluid volumes. Efficacy was tested in the double-hemorrhage dog model of SAH. Nimodipine–PLGA microparticles significantly attenuated angiographic vasospasm. This therapeutic approach shows promise for improving outcome after SAH and may have broader applicability for similar diseases that are confined to body cavities or spaces, are self-limited, and lack effective treatments.     

非开颅蛛网膜下腔出血大鼠脑血流量和水、电解质含量研究

利用非开颅大鼠模型观察蛛网膜下腔出血（ＳＡＨ）后２４ｈ内脑血流量和水电解质含量的动态变化和尼莫地平对其影响。结果发现ＳＡＨ后脑血迅速降低，１ｈ了低值，２４ｈ内持于低水平状态。ＳＡＨ后１ｈ开始脑组织Ｃａ＾２＋答聚，６ｈ后出现脑水肿。尼莫地平对上述指标均有改善作用。提示脑血管痉挛及微循环异常所致脑血流减少在ＳＡＨ继发性的损害中起重要作用，尼莫地平可减轻上述病理改变。     

尼莫地平对蛛网膜下腔出血大鼠额叶转化生长因子-β1表达的影响

目的：探讨尼莫地平对蛛网膜下腔出血（SAH）大鼠额叶转化生长因子-β1（TGF—β1）表达和血管痉挛的影响。方法：枕大池二次注血法制作SAH模型。54只成年健康雄性SD大鼠随机分为对照组（n=6）、SAH组（n=24）和尼莫地平处理组（n=24），其中SAH组和尼莫地平处理组随机均分为1、3、5和7d等4组（n=6）。尼莫地平处理组于二次注血后30min时经股静脉注入尼莫地平2mg／kg，此后每天经腹腔注射尼莫地平2mg／kg。HE染色光镜下观察基底动脉病理学变化，测定内径；免疫组化法检测各组大鼠额叶TGF—β1表达。结果：SAH组和尼莫地平处理组基底动脉内径显著小于对照组（P〈0．01），而SAH组与尼莫地平处理组无显著差异。SAH1d时，TGF—β1表达增加，3d时达高峰，5d和7d时显著低于1d和3d时（P〈0．01），但仍照著高于对照组（P〈0．01）。与SAH组相比，尼莫地平处理组1d和3d时TGF-β1表达无显著差异，5d和7d时显著增加。结论：SAH后额叶TGF—β1表达发生改变，与脑血管痉挛有关，提示TGF-β1参与了脑血管痉挛的病理学过程。尼莫地平可能通过增加SAH后啮组织中TGF-β1表达对缺血脑组织起着保护作用。     

Effect of nimodipine on cerebral blood flow and cerebrovascular reactivity after subarachnoid haemorrhage

The aim of the present study was to investigate the effect of nimodipine on autoregulation of cerebral blood flow (CBF), CO2 reactivity and cerebral oxygen metabolism (CMRO2) in patients with subarachnoid haemorrhage (SAH). Eight patients with severe SAH were studied with repeated CBF and CMRO2 measurements on the first day of the bleeding and after at least 12 h of treatment of nimodipine. An initial resting study, an autoregulation study and a hyperventilation study was performed. CBF was measured using the 133-Xenon intravenous method. CMRO2 was calculated as AVDO2 x CBF. Nimodipine did not significantly change CBF and CMRO2 in the initial resting study. After induced arterial hypotension intact autoregulation was found before as well as after treatment with nimodipine. Beneficial effects of nimodipine were found on CO2 reactivity and CMRO2 during hypotension that may be explained as a positive effect on cerebral ischaemia.     

鼠脑血管痉挛时尼莫地平对体感诱发电位的影响

目的 探讨蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）对体感诱发电位（SEP）的影响,及尼莫地平（ND）的保护作用。方法 对单纯SAH组和ND处理组大鼠观察手术前后基底动脉管径,并检测24h内局部脑血流量（rCBF)、SEP潜伏期及脑组织内皮素-1（ET-1）含量的动态变化。结果 SAH组大鼠在诱导SAH后rCBF立即降低,并持续24h,同时有基底动脉痉挛;SAH后1h开始至24hSEP潜伏期逐渐延长,脑组织ET-1含量显著增加,ND处理组大鼠上述变化均较轻。结论 SAH后CVS可通过脑血流的降低,脑组织ET-1增加而导致SEP潜伏期延长,ND通过拮抗脑组织ET-1变化而对之具有保护作用。     

尼莫地平加脑脊液置换治疗蛛网膜下腔出血的预后

目的观察钙离子拮抗剂尼莫地平加脑脊液置换对蛛网膜下腔出血的临床预后。方法 74例蛛网膜下腔出血患者分为治疗组38例和照组36例。2组入院后即开始泵入尼莫地平,持续14d;治疗组加脑脊液置换治疗,其他治疗同对照组。观察2组的脑血管痉挛发生率及临床预后。结果治疗组脑血管痉挛及临床预后均较对照组显著好转(P<0.05)。结论尼莫地平加脑脊液置换治疗蛛网膜下腔出血可以有效减少脑血管痉挛及改善预后。     

Changes in contractile response and effect of a calcium antagonist, nimodipine, in isolated intracranial arteries of baboon following experimental subarachnoid hemorrhage

Isolated pial arteries from a previously well-characterized model of experimental subarachnoid hemorrhage (SAH) in baboon were tested for their contractile response to 5-hydroxytryptamine (5-HT), norepinephrine (NE), and prostaglandin F2 alpha (PGF2 alpha) and the effect of the calcium antagonist, nimodipine. Autologous blood was injected cisternally at three times with one-day intervals to a total amount of 11.5-29.5 ml (mean: 18.5 ml), and the animals were killed 7 days after the first injection. Untreated animals served as controls. The degree of maximum contraction (EAm) with 5-HT and NE in the control situation was for the three arteries tested in the order middle cerebral greater than anterior cerebral greater than basilar artery. Experimental SAH markedly increased EAm, by 190-370 percent above control values (depending on type of vessel) for 5-HT and 170-185 percent for NE. In addition, the sensitivity to 5-HT was significantly increased, as evidenced by a left-shift of the concentration-response curve. Previous exposure of the artery to 10(-6) M nimodipine reduced the contractile response of both amines to approximately half, the inhibition being slightly less pronounced post-SAH. When vessels were contracted beforehand with the amines or with PGF2 alpha, followed by administration of increasing amount of nimodipine (10(-9) M to 10(-6) M), a concentration-dependent relaxation was obtained by up to 60 percent of the original level. This relaxing effect was significantly less following SAH in the experiments with NE and PGF2 alpha compared to 5-HT; the contraction in the presence of 5-HT did not differ before and after experimental SAH. The experiments show that SAH markedly enhances the intrinsic activity for both 5-HT and NE. Nimodipine inhibits the contractile response less efficiently following experimental SAH. The difference in the responsiveness to 5-HT on the one hand, and to NE and PGF2 alpha on the other, could be due to differences in the blood-induced alterations of those calcium channels that are influenced by the calcium antagonist, nimodipine.