新生大鼠缺氧缺血性脑病脑组织氨基酸含量变化及脑活素的治疗作用

本文旨在研究脑组织中氨基酸含量与新生大鼠缺氧缺血性脑病(HIE)发病机制的关系及脑活素的治疗机制,在建立新生大鼠HIE模型的基础上,采用氨基酸自动分析仪检测103例大鼠左侧顶叶脑组织氨基酸含量,并研究脑组织病理改变,同时通过侧脑室及肌肉两种途径给予脑活素(2.5mL·kg~(-1))治疗,每日一次,观察72h。结果显①HIE组脑组织兴奋性氨基酸(EAA)(谷氨酸、天门冬氨酸)含量明显增高,P<0.01,以缺氧缺血后48h EAA含量最高;②脑活素治疗组在侧脑室及肌肉注射脑活素治疗48h时,EAA含量均明显低于同期各HIE对照组,差异显著,P<0.01。与正常对照组比较,治疗后24h及48h存在差异(P<0.01),治疗72h后差异无显著意义(P>0.01)。③侧脑室及肌肉注射脑活素后24h,两组脑组织中EAA含量差异无显著意义(P>0.05);48h后,两组出现差异,P<0.05。结论①脑组织兴奋性氨基酸含量异常升高与缺氧缺血性脑病的发病机制有一定关系。②脑活素治疗HIE的机制可能与其显著降低脑组织中EAA含量有关。③侧脑室注射脑活素和肌肉注射脑活素的治疗效果存在一定的差异。     

缺氧缺血性脑病新生大鼠脑内单胺类神经递质的改变

目的研究新生儿缺氧缺血性脑病(HIE)的发病机制。方法制作新生大鼠HIE模型,用高效液相电化学法检测脑组织单胺类神经递质含量。结果HIE组结扎侧单胺类神经递质含量明显增加,与结扎对侧及正常对照组相比有显著性差异(P＜0.01)。结论单胺类神经递质参与了HIE的病理生理过程。     

新生大鼠缺氧缺血性脑病脑组织氨基酸含量变化及脑活素的治疗作用

本文旨在研究脑组织中氨基酸含量与新生大鼠缺氧缺血性脑病(HIE)发病机制的关系及脑活素的治疗机制,在建立新生大鼠HIE模型的基础上,采用氨基酸自动分析仪检测103例大鼠左侧顶叶脑组织氨基酸含量,并研究脑组织病理改变,同时通过侧脑室及肌肉两种途径给予脑活素(2.5 mL@kg-1)治疗,每日一次,观察72 h.结果显①HIE组脑组织兴奋性氨基酸(EAA)(谷氨酸、天门冬氨酸)含量明显增高,P＜0.01,以缺氧缺血后48 h EAA含量最高;②脑活素治疗组在侧脑室及肌肉注射脑活素治疗48 h时,EAA含量均明显低于同期各HIE对照组,差异显著,P＜0.01.与正常对照组比较,治疗后24h及48h存在差异(P＜0.01),治疗72 h后差异无显著意义(P＞0.01).③侧脑室及肌肉注射脑活素后24 h,两组脑组织中EAA含量差异无显著意义(P＞0.05);48 h后,两组出现差异,P＜0.05.结论①脑组织兴奋性氨基酸含量异常升高与缺氧缺血性脑病的发病机制有一定关系.②脑活素治疗HIE的机制可能与其显著降低脑组织中EAA含量有关.③侧脑室注射脑活素和肌肉注射脑活素的治疗效果存在一定的差异.     

一氧化氮在新生大鼠缺氧缺血性脑病中的变化及作用探讨

新生儿缺氧缺血性脑病发病率高,致残率和致死率均较高,关于其发病机制仍未完全阐明,本文利用新生大鼠制成HIE模型,探讨NO在HIE发病机制中的作用。材料及方法一、材料 生后七日SD大鼠乙醚麻醉,     

缺氧缺血性脑病大鼠脑内兴奋性氨基酸含量动态变化

目的 观察缺氧缺血后新生鼠脑组织中谷氨酸（Glu)、天冬氨酸（Asp) 含量的动态变化。方法 56只新生大鼠随机分成7组，吸入8％氧气和92％氮气混合气体建立缺氧缺血性脑病（HIE）模型，观察各部分脑组织中Glu、Asp含量的变化。结果 缺氧缺血30min后Glu、Asp含量开始增加，与对照组相比存在明显差异（P＜0．05），在缺氧缺血后60、120 min时，与对照组相比仍存在明显差异（P＜0．01），24h脑组织中Glu 、Asp含量仍升高，与对照组相比无差异（P＞0．05），至48h Glu、Asp含量已基本恢复正常水平，且各部分脑组织间无明显差异。结论 缺氧缺血后兴奋性氨基酸先明显增加，随后逐渐减低，直至恢复正常水平。     

浅谈新生儿缺氧缺血性脑病

由于各种围生因素引起的缺氧和脑血流减少，导致胎儿和新生儿的脑损伤，称之为缺氧缺血脑病(hypox—ischemic encephalopathy HIE)。发生在围产儿，尤其是足月儿多见，其病死率和致疾率极高，目前我国围产儿死亡原因中以胎婴儿畸形为主，其次是新生儿     

高压氧治疗新生大鼠缺氧缺血性脑病

４９只新生大鼠ＨＩＥ模型分成高压氧治疗组和对照组，分别于模型制作后４８小时及七天处死，观察脑大体改变和脑含水量。结果显示，采用２．３ＡＴＡ治疗三次有明显减轻脑水肿及脑软化作用。     

脑多肽治疗新生儿缺氧缺血性脑病45例疗效观察

新生儿缺氧缺血性脑病(HIE)是围产期新生儿常见的颅内病变,自1997年1月～1997年12月我科对45例HIE患儿应用支持疗法及对症处理,并加用脑多肽治疗,现报告如下。 临床资料 一、病例选择 101例HIE患儿均符合杭州会议制定的HIE临床诊断依据和分类标准,并经头颅CT扫描证实。其中1996年1月～1996年12月期间住院病例共56例为对照组,男39例,女17例;早产儿9例,足月儿47例;体重<     

新生儿缺氧缺血性脑病的发病机制和防治进展

围生期窒息所致缺氧缺血性脑病（hypoxic-ischemicencepholopathy,HIE）为新生儿期危害最大的常见病之一,常引起新生儿死亡和其后神经系统的发育障碍。估计约有0．2％～0．4％的足月儿和60％的早产儿或小于胎龄儿围生期窒息,其中10％～60％可在新生儿期死亡,25％的存活儿可呈现永久性脑损害如脑瘫、癫痛、智力低下、学习困难及视听障碍等临床后遗症。我国每年出生的新生儿中,则有7％～IO％（140万～200万）的新生儿发生窒息,其中约1／3的窒息儿死亡,30万左右的窒息儿出现不同程度的残疾,后果极为严重。如何早期诊断、合理治疗乃至…     

围产期不良事件致新生儿急性缺氧缺血性脑损伤的类型分析

目的 探讨围产期不良事件致新生儿急性缺氧缺血性脑损伤（HIBI）的临床及影像学特征。方法 选取2004~2013 年46 例HIBI 患儿,对其临床及脑损伤类型进行分析。结果 足月儿组脑白质损伤为95%、皮层损伤90%、基底节- 丘脑损伤75% 和脑干损伤65%。早产儿组脑白质损伤73%、皮层损伤23%、基底节- 丘脑损伤19%、脑干损伤15%。早产儿灰质损伤发生率均低于足月儿组（P<0.05）;46% 的急性HIBI患儿伴有多器官功能受累,足月儿组临床表现较典型,95% 符合中、重度脑病,影像学改变多为混合型损伤,且以中、重度基底节- 丘脑损伤为主（68%）。多器官受累及动脉血pH 值小于7.1 与中、重度脑损伤的发生密切相关。结论 白质损伤是最常见的HIBI 类型,早产儿组也可见灰质损伤,但发生率低。中、重度脑病患儿的影像学损伤程度较重,且以基底节- 丘脑损伤为主。多器官受累、异常神经系统表现及早期血气分析对新生儿HIBI 诊断尤为重要。     

Prolonged seizures exacerbate perinatal hypoxic-ischemic brain damage

This study was undertaken to clarify whether seizures in the newborn cause damage to the healthy brain and, more specifically, to determine the extent to which seizures may contribute to the brain-damaging effects of hypoxia-ischemia (HI). Seizures were induced in 10-d-old rat pups with kainic acid (KA). Seizure duration was determined electrographically. HI was induced by common carotid artery ligation followed by exposure to 8% oxygen for either 15 or 30 min. Six groups of animals were assessed: 1) controls [neither KA nor HI (group I)]; 2) group II, KA alone; 3) group III, 15 min HI alone; 4) group IV,15 min HI plus KA; 5) group V, 30 min HI alone; and 6) group VI, 30 min HI plus KA. Animals were assessed neuropathologically at 3 (early) and 20 (late) d of recovery. KA injection without hypoxia resulted in continuous clinical and electrographic seizures lasting a mean of 282 min. No neuropathologic injury was seen in groups I (no HI or KA), II (KA alone), III (15 min HI alone), or IV (15 min HI and KA). Animals in group V (30 min HI alone) displayed brain damage with a mean score of 2.3 and 0.60 at 3 and 20 d of recovery, respectively. Animals in group VI (30 min HI and KA) had a mean score of 12.1 and 3.65 at 3 and 20 d of recovery, respectively. Compared with group V, the increased damage as a result of the seizure activity in group VI occurred exclusively in the hippocampus. Status epilepticus in the otherwise "healthy" neonatal brain does not cause neuropathologic injury. However, seizures superimposed on HI significantly exacerbate brain injury in a topographically specific manner.     

缺氧缺血性脑损伤新生大鼠脑组织基质金属蛋白酶的动态变化及对细胞凋亡的影响

目的探讨缺氧缺血性脑损伤(HIBD)新生大鼠脑组织基质金属蛋白酶(MMPs)的动态变化及其与细胞凋亡的关系。方法将72只7日龄W istar大鼠随机分为假手术组和HIBD组,后者根据处死时间分为6 h、24 h、48 h、5天和14天组,每组12只。采用免疫组化方法测定MMP-2、MMP-9和金属蛋白酶组织抑制因子-1(TIMP-1)的表达,用流式细胞术测定脑细胞凋亡率。结果 HIBD组缺氧缺血侧大脑组织MMP-2于损伤6 h增高,5天再次升高,且峰值高于6 h组,与假手术组相比,除24 h组,其余差异均有统计学意义(P<0.05);MMP-9正常情况下有一定表达,HIBD 24 h表达达高峰,后逐渐下降,与假手术组相比,除14天组,差异均有统计学意义(P<0.05);TIMP-1正常情况下与MMP-9保持动态平衡,HIBD时两者比例失衡,后期表达增加两者平衡恢复,与假手术组相比,除6 h组和14天组,差异均有统计学意义(P<0.05)。HIBD组缺氧缺血侧脑细胞凋亡率24 h轻度升高,5天达高峰,与假手术组相比,除6 h组,差异均有统计学意义(P<0.05)。结论新生大鼠HIBD后MMP-2、MMP-9和TIMP-1的表达有不同程度变化,可能参与了HIBD的发病与修复。     

Cerebral blood flow and edema in perinatal hypoxic-ischemic brain damage

The relationship between cerebral blood flow (CBF) and the evolution of brain edema was investigated in an experimental model of perinatal hypoxic-ischemic brain damage. Seven-d postnatal rats were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen at 37 degrees C. This insult produces neuronal necrosis and/or infarction only in the cerebral hemisphere ipsilateral to the arterial occlusion in the majority of animals; hypoxia alone produces no damage. CBF, measured by the indicator diffusion technique using iodo[14C]-antipyrine, and tissue water content were determined concurrently in both cerebral hemispheres at specific intervals during recovery from cerebral hypoxia-ischemia. Water contents in the ipsilateral cerebral hemisphere were 89.1, 89.6, 89.7, 91.0, and 88.3% at 30 min, 4 h, 24 h, 3 d, and 6 d, respectively (p less than 0.001); whereas the percent tissue water in the contralateral hemisphere was unchanged from values in nonligated, hypoxic control rats (87.7%). CBF was similar in both cerebral hemispheres at 30 min, 4 h, and 24 h of recovery (50-65 mL/100 g/min) and not different from age-matched controls. At 3 and 6 d, CBF in the ipsilateral cerebral hemisphere was 30 and 26% of the contralateral hemisphere and 23 and 29% of the control animals, respectively (p less than 0.001). No inverse correlation existed between the changes in brain water content and CBF at any interval until 6 d of recovery. Thus, an early hypoperfusion does not follow perinatal cerebral hypoxia-ischemia, as occurs in adults.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neurobiology of hypoxic-ischemic injury in the developing brain

Hypoxic ischemia is a common cause of damage to the fetal and neonatal brain. Although systemic and cerebrovascular physiologic factors play an important role in the initial phases of hypoxic-ischemic injuries, the intrinsic vulnerability of specific cell types and systems in the developing brain may be more important in determining the final pattern of damage and functional disability. Excitotoxicity, a term applied to the death of neurons and certain other cells caused by overstimulation of excitatory, mainly glutamate, neurotransmitter receptors, plays a critical role in these processes. Selected neuronal circuits as well as certain populations of glia such as immature periventricular oligodendroglia may die from excitotoxicity triggered by hypoxic ischemia. These patterns of neuropathologic vulnerability are associated with clinical syndromes of neurologic disability such as the extrapyramidal and spastic diplegia forms of cerebral palsy. The cascade of biochemical and histopathologic events triggered by hypoxic ischemia can extend for days to weeks after the insult is triggered, creating the potential for therapeutic interventions.     

Effect of glucose on perinatal hypoxic-ischemic brain damage.

Investigations suggest that hyperglycemia superimposed on hypoxia-ischemia or cerebral ischemia accentuates brain damage in adult experimental animals and humans. Such does not appear to be the case in immature animals. The present review discusses fundamental differences in immature and adult brain metabolism which account for the age-specific paradox. Based on currently available data, it is recommended that glucose supplementation not be curtailed during labor and delivery of asphyxiated human infants; on the contrary, glucose therapy might substantially reduce hypoxic-ischemic brain damage.     

围产期缺氧缺血性脑损伤影像学诊断的意义

影像学检查是围产期缺氧缺血性脑损伤临床诊治及研究不可缺少的手段 ,最常用于颅内疾病诊断的方法是B超 ,CT ,MRI。诊断基础是疾病的病理过程 ,可在活体上直观地了解脑结构的变化 ,包括脑损伤的类型、部位、程度及病变过程。损伤早期脑水肿为主要病理变化 ,B超和CT影像特征分别为强回声和低密度。 7～ 10d后 ,B超检查强回声持续不退 ,分布不均匀并伴脑室形态变化 ,预示脑内可能遗留病变。后遗病变期 ,影像检查显示出不同部位的脑萎缩及囊性变。小儿出生后即显示脑损伤晚期变化影像特征 ,意味损伤发生在胎儿期。MRI检查对脑白质发育问题的诊断具有重要意义。脑结构与功能相结合的新型影像检查技术为脑科学的发展提供了广阔空间     

Predicting outcome in hypoxic-ischemic brain injury.

Predicting the neurologic outcome of children after a hypoxic-ischemic event continues to be a challenge for intensivists and pediatric neurologists. Nevertheless, with accurate history taking, serial neurologic examination, and some ancillary studies, the clinician can predict accurately whether a child will die or have profound neurologic damage. Aggressive resuscitation should be offered to all children when found in CPA. A simple ingestion might have led to this clinical scenario, and complete neurologic recovery may be possible if effective resuscitation is implemented. In cases of drowning, several factors, if present, are consistent with profound neurologic sequelae or death. These include prolonged submersions with asystole, delayed onset of CPR, no spontaneous respirations on arrival to the emergency department, and low initial pH value. The options of withdrawal of life support or a DNR status should be offered to families of children who have survived a devastating hypoxic-ischemic event but who are in a PVS. If brain-death criteria have been fulfilled, the patient must then be disconnected from life support after organ donation has been discussed with the family.     

MRI of perinatal brain injury

MRI is invaluable in assessing the neonatal brain following suspected perinatal injury. Good quality imaging requires adaptations to both the hardware and the sequences used for adults or older children. The perinatal and postnatal details often predict the pattern of lesions sustained and should be available to aid interpretation of the imaging findings. Perinatal lesions, the pattern of which can predict neurodevelopmental outcome, are at their most obvious on conventional imaging between 1 and 2 weeks from birth. Very early imaging during the first week may be useful to make management decisions in ventilated neonates but brain abnormalities may still be subtle using conventional sequences. Diffusion-weighted imaging (DWI) is very useful for the early identification of ischaemic tissue in the neonatal brain but may underestimate the final extent of injury, particularly basal ganglia and thalamic lesions. MR imaging is an excellent predictor of outcome following perinatal brain injury and can therefore be used as a biomarker in interventional trials designed to reduce injury and improve neurodevelopmental outcome.