缺氧/缺血对幼龄大鼠脑少突胶质细胞的影响

目的探讨缺氧和(或)缺血对幼龄大鼠脑白质损伤及脑损伤后少突胶质细胞(OL)的影响。方法选择3日龄同窝生SD低龄新生大鼠128只,随机分为4组:缺氧缺血组、单纯缺血组、单纯缺氧组、对照组。建立未成熟鼠缺氧缺血脑损伤模型,采用组织切片HE染色、OL抗体O4和细胞凋亡免疫组织化学双标记方法,观察各组脑损伤新生大鼠脑组织的形态学变化。结果缺氧和(或)缺血引起幼龄大鼠脑组织损伤,以白质损伤为主,出现白质疏松和脑室扩大等病理变化,深部脑白质OL凋亡数增多(P<0.05)。缺氧或缺血单因素均可诱导OL数减少,并发生凋亡,缺氧、缺血二因素存在协同作用(P<0.01),但缺血较缺氧对新生大鼠脑OL细胞的促凋亡作用更明显,术后48h和72h效应指数分别为7.34/2.42和7.15/1.89。结论缺氧和(或)缺血均可导致脑白质损伤及OL凋亡增多,缺血较缺氧促OL凋亡更明显,缺氧缺血存在协同作用。     

黄芪和美金胺对缺氧缺血再灌注后脑内血小板活化因子生成量的影响

围产期窒息所致缺氧缺血性脑损伤是造成新生儿死亡和其后神经系统后遗症的主要原因。近来研究显示,在缺氧缺血再灌注损伤阶段,作为一种活跃的脂类炎性调节因子,血小板活化因子(PAF)对于自由基的大量生成,进一步加剧缺氧缺血性脑损伤起了关键作用。本研究在成功创建新生大鼠缺氧缺血再灌注损伤模型的基础上,对新生大鼠脑     

缺氧缺血新生鼠脑早期微循环改变的形态学研究

目的　 观察缺氧缺血性脑损伤时新生鼠脑早期微循环的形态学改变。 方法 　在缺氧缺血性脑损伤的动物模型上 ,采用组织化学染色及脑组织墨汁灌注观察脑组织血管形态和分布。 结果 　缺氧缺血后即刻脑皮质、髓质、海马微血管数增多 ,微血管通透性增强 ,微血管内血栓形成 ,脑内多部位出血 ,同时神经元出现水肿、丢失、胶质细胞增生等一系列缺血缺氧改变。结论 　缺氧缺血性脑损伤时早期存在着脑微循环障碍 ,在临床缺血缺氧性脑损伤的救治过程中应注意尽早纠正     

新生大鼠缺氧缺血性脑损伤1,4,5—三磷酸肌醇的变化研究

为探讨缺氧缺血性脑损伤时脑第二信使１,４,５－三磷酸肌醇（ＩＰ３）变化,本研究在生后７日龄新生大鼠缺氧缺血性脑病损伤动物模型上采用放射蛋白竞争结合法进行ＩＰ３测定,结果显示：正常生后７,８,９日新生大鼠脑额脑皮质,海马及丘脑ＩＰ３含量不同,生后７日龄新生大鼠缺氧缺血后额离皮质,海马ＩＰ３降低,丘脑ＩＰ３升高,动态观察上述变化以缺氧缺血后７２小时明显,２４小时之内显著,提示：缺氧缺血性脑损伤时脑第二     

缺氧缺血新生鼠脑早期微循环改变的形态学研究

目的：观察缺氧缺血性脑损伤时新生鼠脑早期微循环的形态学改变，方法：在缺氧缺血性脑损伤的动物模型上，采用组织化学染色及脑组织墨汁灌注观察脑组织血管形态和分布，结果：缺氧缺血后即刻脑皮质，髓质，海马微血管数增多，微血管通透性增强，微血管内血栓形成，脑内多部位出血，同时神经元出现水肿，丢失，胶质细胞增生等一系列缺血缺氧改变，结论：缺氧缺血性脑损伤时早期存在着脑微循环障碍，在临床缺血缺氧性脑损伤的救治过程中应注意尽早纠正。     

高血糖与围生期缺氧缺血性脑损伤（综述）

多年以前进行的研究表明,用葡萄糖预处理围生期动物,当它们受到全身缺氧、窒息或脑缺血时,能够延长其生存期并可减轻永久性脑损伤的程度。但在成年动物的试验显示,补充葡萄糖实际上加重缺血缺氧性脑损伤。因此,葡萄糖在缺氧缺血中存在一个矛盾现象:一方面延长新生动物缺氧后生存期,另一方面在成年动物加重其脑损伤。     

缺氧缺血脑组织生化免疫成分的改变

探讨缺氧缺血性脑损伤的病理生理机制能为其临床干预提供较为有力的依据。本文从缺氧缺血后脑组织的生化物质代谢水平、基因调控水平和免疫分子水平几个方面的改变来阐述缺氧缺血性脑损伤的发病机制,揭示缺氧缺血所致的脑组织损伤和抗损伤的矛盾变化。     

镁对缺氧缺血性脑损伤保护作用的研究进展

镁对缺氧缺血引起的脑损伤有保护作用 ,但作用机制尚未阐明。现就镁对缺氧缺血性脑损伤保护作用的研究进展、作用机制以及新生儿临床应用中存在的问题综述如下。一、镁对缺氧缺血性脑损伤的保护作用人和啮齿类动物脑对缺氧缺血都非常敏感 ,受损区域常为皮质、海马ＣＡ1区、纹状体。动物实验已证实镁能抑制缺氧缺血性脑损伤。Ｎｉｓｈｉｋｉ等[1] 在脑缺血处理前给新生鼠腹膜内注射硫酸镁 ,发现注射 6 0ｍｉｎ后即能减少脑皮质梗塞面积。Ｍａｒｉｎｏｖ等[2 ] 研究表明 ,脑缺血前给鼠颈动脉内注射硫酸镁 ,对暂时性脑缺血有强大的神经保护作用…     

脑源性神经营养因子与脑缺血缺氧的研究进展

脑缺血缺氧损伤后,脑源性神经营养因子（BDNF）及其受体TrKB基因表达增加,尤其以梗死灶周围和海马区更突出。BDNF通过维持细胞内Cα^2 稳定、清除自由基、阻滞细胞凋亡,以实现其保护神经元免受缺血缺氧的损伤,内源性BDNF是抵御缺血缺氧脑损伤的内在保护剂,外源性BDNF能增加梗死区神经元的存活数并促进脑功能的恢复,在脑发育早期具有更强的神经保护作用。     

HIE新生儿肾功能指标变化与阴离子间隙、血渗透压的关系

HIE是多种原因导致脑缺氧缺血而出现的脑损伤.严重缺氧也可引起新生儿多器官缺氧缺血性损害,肾脏是极为常见的脏器之一.     

地塞米松对脑缺氧缺血大鼠bid基因表达及细胞凋亡的影响

目的 探讨新生大鼠缺氧缺血性脑损伤（HIBD）后bid基因表达及细胞凋亡的变化，地塞米松（DEX）对其的调控作用，从而阐明DEX预处理对缺氧缺血新生动物神经保护作用的可能机制。方法 7d龄SD大鼠24只。随机分成DEX组、9g／L盐水组（NS组）、HIBD组、健康对照组。DEX和NS组在缺血缺氧前12h腹腔内分别注射DEX、等量NS。通过建立新生大鼠HIBD动物模型，取实验侧大脑半球，采用RT-PCR技术检测脑bid基因表达，采用Tunel法检测凋亡细胞。结果 正常组无bid基因表达，HIBD组bid基因表达明显上调，凋亡细胞数明显增加（P〈0．01）；与HIBD组比较，DEX组bid基因表达明显下调，而凋亡细胞数明显减少（P〈0．01）。结论 脑缺氧缺血引起神经细胞凋亡可能与bid基因表达明显上调有关。DEX能通过下调bid基因表达，从而抑制细胞凋亡，起到神经保护作用。     

诱导型一氧化氮合酶和缺氧缺血脑损伤

缺氧缺血可导致严重的神经系统疾病,如脑卒中、新生儿缺氧缺血性脑病。诱导型一氧化氮合酶在缺氧、缺血过程中被诱导表达,产生过量一氧化氮,导致神经系统的炎症反应及神经元死亡,加重神经损伤。抑制诱导型一氧化氮合酶表达在体内体外实验及临床应用中显示了一定的神经保护作用。该文综述了诱导型一氧化氮合酶在中枢神经系统中的表达及与缺氧缺血脑损伤的相关性,展望了诱导型一氧化氮合酶抑制剂作为缺氧缺血脑损伤治疗策略的前景。     

地塞米松对脑缺氧缺血新生大鼠细胞凋亡抑制蛋白1 mRNA及Caspase-3活性的影响

目的：探讨新生大鼠缺氧缺血性脑损伤（HIBD）后细胞凋亡抑制蛋白1（cIAP1）基因表达、Caspase-3活性的变化及地塞米松（DEX）对其影响，阐明DEX预处理对HIBD神经保护的可能机制。方法：7日龄SD大鼠24只，随机分成DEX组、9g／L盐水组（NS组）、HIBD组、健康对照组。DEX、NS、HIBD组大鼠采用Rice方法制备HIBD模型。DEX和NS组在缺氧缺血前12h腹腔内分别注射DEX、等量9g／L盐水。取HIBD动物模型实验侧大脑半球，采用逆转录-聚合酶链反应（RT-PCR）检测cIAP1基因表达，比色法测定Caspase-3活性。结果：与健康对照组比较，HIBD组大鼠cIAP1基因表达明显下降（P〈O．01），Caspase-3活性明显上升（P〈0．01）。与HIBD组比较，DEX组cIAP1基因表达明显上升，而Caspase-3活性明显下降。结论：脑缺氧缺血可导致cIAP1基因表达下调，Caspaes-3活性升高。DEX能通过上调cIAP基因表达，抑制Caspase-3活性，抑制细胞凋亡，起到神经保护作用。     

促红细胞生成素对缺氧缺血新生鼠脑匀浆一氧化氮及血浆内皮素的影响

目的探讨体外注射重组人促红细胞生成素(rhEPO)对新生鼠缺氧缺血后脑组织一氧化氮(NO)和NO合成酶(NOS)及血浆内皮素(ET)水平的影响,阐明其对缺氧缺血(HI)新生动物神经保护作用的机制。方法将7日龄SD大鼠制备缺氧缺血脑损伤(HIBD)模型及rhEPO治疗模型,将假手术组作对照。测定各组新生鼠HI后6 h脑组织匀浆NO和NOS含量以及血浆ET水平。结果HIBD组在HI后6 h脑组织NO、NOS及血浆ET均升高(P<0.05),rhEPO组脑组织NO、NOS显著降低水平(P<0.05),而血浆ET含量无明显改变。结论外源性rhEPO可通过减少NO的过量生成而对HIBD后的脑组织起到保护作用。     

Development of acute edema following cerebral hypoxia-ischemia in neonatal compared with juvenile rats using magnetic resonance imaging

We hypothesized that the evolution of cerebral edema accompanying cerebral hypoxia-ischemia is dependent on age and that such differences would be detectable using magnetic resonance imaging methods. Thus we examined in immature and juvenile rats the relationship between hypoxic-ischemic changes in T1 and T2 and the alterations in brain water content, as assessed by differences in tissue wet-dry weights. One- and 4-wk-old rats were anesthetized and subjected to unilateral carotid artery occlusion and subsequent exposure to hypoxia (8% oxygen). T1 and T2 maps were acquired at 9.4 T, and then brain water content was measured in sham controls or in hypoxic-ischemic animals before, during, and 1 or 24 h after hypoxia-ischemia. In sham controls, T1, T2, and proton density decreased with increasing age, corresponding to an ontogenic decrease in water content. In 1-wk-old rats, increases in T1 and T2 were observed during and at 1 and 24 h after hypoxia-ischemia, corresponding to elevations in water content. In 4-wk-old rats, T1 and water content increased during and at 1 and 24 h after hypoxia-ischemia whereas T2 was not increased until 24 h after hypoxia-ischemia. Regression analysis showed that T1 correlated better with total water content than T2. In both immature and older brain, an increase in total brain water develops acutely and persists after an episode of cerebral hypoxia-ischemia, and T1 imaging detects this change better than T2. Hypoxic-ischemic changes in T2 are age dependent, reflecting other physicochemical changes of water in the tissue than water content alone.     

Dexamethasone prevents hypoxic-ischemic brain damage in the neonatal rat

Glucocorticoid therapy is frequently used in perinatology and neonatology for its beneficial pulmonary effects. We investigated the influence of neonatal glucocorticoid administration on brain damage caused by a concurrent episode of cerebral hypoxia-ischemia. Various doses of dexamethasone in several treatment schedules were administered to 7-d-old rats that were also subjected to unilateral cerebral hypoxia-ischemia. In 79% of control rats, a large unilateral cerebral infarction occurred, whereas all rats pretreated with dexamethasone in doses of 0.01 to 0.5 mg/kg/d for 3 d had no infarction (p less than 0.001). The neuroprotective effect of dexamethasone pretreatment was dose- and time-dependent. Treatment with dexamethasone after the insult or with lower doses before the insult did not prevent infarction. The neuroprotective effect was not immediate: single doses 0 to 3 h prehypoxia were not effective but a single dose 24 h before hypoxia-ischemia prevented cerebral infarction. The results demonstrate that glucocorticoid administration in the neonatal period, even in low doses, protects the brain during subsequent periods of hypoxia-ischemia.     

Proposing a care practice bundle for neonatal encephalopathy during therapeutic hypothermia

Neonates with neonatal encephalopathy (NE) often present with multi-organ dysfunction that requires multidisciplinary specialized management. Care of the neonate with NE is thus complex with interaction between the brain and various organ systems. Illness severity during the first days of birth, and not only during the initial hypoxia-ischemia event, is a significant predictor of adverse outcomes in neonates with NE treated with therapeutic hypothermia (TH). We thus propose a care practice bundle dedicated to support the injured neonatal brain that is based on the current best evidence for each organ system. The impact of using such bundle on outcomes in NE remains to be demonstrated.     

Magnetic resonance imaging during cerebral hypoxia-ischemia: T2 increases in 2-week-old but not 4-week-old rats

We investigated whether the changes detectable with magnetic resonance imaging techniques during and after an episode of cerebral hypoxia-ischemia differ in immature and older brain. Diffusion weighted (DW) and T2-weighted (T2W) images were repeatedly acquired before, during, and after an episode of cerebral hypoxia-ischemia (unilateral carotid artery occlusion plus hypoxia) in 2- and 4-wk-old rats lightly anesthetized with isoflurane. Areas of increased brightness were detected in DW images from both 2- and 4-wk-old rats by 10-20 min after the start of hypoxia. These hyperintense areas increased during hypoxia, comprising 60.8+/-4.9% and 30.5+/-2.7% of the brain image at the level of the thalamus in 2-wk-old and 4-wk-old animals, respectively (p < 0.003). Hyperintense areas (e.g. 27.0+/-8.3%) also appeared in T2W images during hypoxia-ischemia in 2-wk-old animals, but these did not occur in 4-wk-old animals (p < 0.02). This observation was reflected in T2, which increased during hypoxia-ischemia in the 2-wk-old but not the 4-wk-old group. By 60 min after the termination of hypoxia-ischemia in either age group, areas of hyperintensity resolved and then reappeared 24 h later on both DW and T2W images. Thus, irrespective of age, magnetic resonance imaging changes during transient hypoxia-ischemia generally recover with a delayed or secondary increase in DW and T2W hyperintensity hours later. Immature brain differs from older brain primarily with respect to some combination of hypoxic/ischemic cellular or biochemical changes, that are detectable as increases in T2 within 2-wk-old but not 4-wk-old animals.     

缺氧缺血后新生鼠脑组织caspase-3mRNA表达变化及其意义

目的　观察新生大鼠缺氧缺血后脑组织caspase 3mRNA表达动态变化 ,进一步探讨缺氧缺血诱导新生鼠神经元凋亡的机制及意义。方法　制备新生鼠HIBD模型 ,随机分为假手术对照组、HIBD 6h、2 4h、3d、5d组 ,每组 5只动物。应用RT PCR方法测定了大鼠脑组织caspase 3mRNA的表达。结果　 7日龄Wistar大鼠假手术对照组即有一定水平caspase 3mRNA表达 ,HIBD 6h组表达增加(与对照组比较有显著性差异 ,P <0 0 5 ) ,HIBD 2 4h其表达呈高峰 ,此后逐渐下降 ,HIBD 5d仍维持较高水平 (与HIBD 6h相比有显著性差异 ,P <0 0 1)。结论　缺氧缺血可诱导新生鼠脑组织caspase 3mRNA表达 ,其过度表达在HIBD后神经元凋亡的调控中起一定作用 ,针对caspase 3的治疗对策为围生期缺氧缺血脑损伤打开了新视窗     

The influence of growth retardation on perinatal hypoxic-ischemic brain damage

The effect of growth retardation on the extent of brain damage produced by hypoxia-ischemia was assessed in immature rats. Newborn rats were raised in litters of 6 or 14 pups from day 2 to 7. On postnatal day 7, those immature rats raised in litters of 14 weighed 18% less than animals raised in litters of 6 (P less than 0.001). They then were subjected to cerebral hypoxia-ischemia by unilateral common carotid artery ligation followed by 3 h of exposure to 8% oxygen-92% nitrogen at 37 degrees C. Upon return to their dams, all litters were culled to 6 pups. At 30 days of age, the animals underwent perfusion-fixation of their brains under pentobarbital anesthesia. Brain damage was assessed by measuring the length and width of each cerebral hemisphere. The extent of brain damage varied from no difference in the size of the two cerebral hemispheres to marked shrinkage of the hemisphere ipsilateral to the common carotid artery occlusion. The range of brain damage between the well-nourished and poorly nourished animals was comparable. Rank order of the extent of damage demonstrated significantly greater tissue injury in those animals well nourished prior to hypoxia-ischemia (Mann-Whitney U-test; P = 0.003). The results indicate that nutritional deprivation in the immature rat is associated with a decreased rather than increased susceptibility to brain damage arising from hypoxia-ischemia. The findings of the investigation have relevance to the human infant suffering from intrauterine growth retardation (IUGR).