脑缺血缺氧后大鼠外周血淋巴细胞热休克蛋白70的表达

目的 研究大鼠缺氧缺血性脑损伤后海马区脑组织病理学损伤变化和外周血单个核细胞的热休克蛋白(HSP)70的表达.方法 建立大鼠脑缺氧缺血模型,苏木素-伊红(HE)染色,光镜下观察脑组织病理学损伤的变化,采用流式细胞术(FCM)检测外周血淋巴细胞HSP70.结果 在缺氧缺性脑损伤后, 外周血淋巴细胞的HSP70水平迅速升高,24 h达到高峰51.05±2.27,其后逐渐降低14.13±1.04至正常水平(P＜0.01),与脑组织病理损伤的时序变化相一致.结论 运用FCM检测外周血淋巴细胞HSP70水平可以作为反映缺氧缺血后脑损伤的辅助指标.     

Exercise-induced changes in branched chain amino acid/aromatic amino acid ratio in the rat brain and plasma

Central fatigue was induced by running rats on a treadmill. Amino acid and ammonia metabolism in the brain and blood were followed with time to correlate its changes with physical exhaustion. The blood ammonia level did not change during running, but was prominently increased at exhaustion. The brain level of ammonia was also prominently high at the end of exercise with a time course of change similar to that of the blood level. Plasma concentrations of branched chain amino acids (BCAA) and aromatic amino acids (AAA) increased as the animals continued to run; however, the plasma BCAA/AAA ratio was definitely depressed at exhaustion. This was also true with the brain BCAA/AAA ratio. A positive correlation was demonstrated between the plasma and brain BCAA/AAA ratios at r=0.5040 and P less than 0.05. These exercise-related changes suggest that physical exercise-induced central fatigue involves not only an increase in brain ammonia, but also a disturbance in brain amine metabolism accompanying plasma and brain BCAA/AAA ratio depression. Furthermore, the ammonia level and BCAA/AAA ratio in the brain correlated with those in the blood. It is reasonable to consider that the blood ammonia concentration and plasma BCAA/AAA ratio may serve as important indices of the clinical condition of exercise-induced central fatigue.     

The aluminum-induced increase in blood-brain barrier permeability to delta-sleep-inducing peptide occurs throughout the brain and is independent of phosphorus and acetylcholinesterase levels

The effect of aluminum on levels of inorganic phosphorus and acetylcholinesterase in blood and brain and on permeability of the blood-brain barrier (BBB) in different regions of the brain to the neuropeptide deltasleep-inducing peptide (DSIP) was studied in adult rats. Aluminum (100 mg/kg) significantly increased the permeability of the BBB to intracarotid ¹²⁵I-N-Tyr-DSIP so that levels of radioactivity in whole brain were 45% higher than in control animals. The pattern of regional distribution of radioactivity in the brain was, however, unaffected, demonstrating that the affect of aluminum occurs throughout the BBB. Aluminum also significantly decreased inorganic phosphorus levels in the serum by 19%, but this effect did not correlate with BBB permeability to DSIP. Aluminum did not decrease brain levels of phosphorus despite the drop in blood levels of phosphorus nor affect brain or blood levels of acetylcholinesterase. Experiments with radioactive ³²P reinforced the finding that blood but not brain levels of phosphorus are reliably affected by aluminum. The lack of correlation between changes in BBB permeability and decreased levels of inorganic phosphorus in the blood suggests that the effect of aluminum may not be mediated by its effects on phosphorus metabolism. Also, the change in BBB permeability after administration of aluminum does not appear to depend on changes in brain cholinergic activity but does occur throughout the brain.     

艾滋病患者脑部病变MRI表现分析

目的探讨艾滋病的脑部MRI表现,总结其影像特征。方法对9例临床疑似艾滋病患者经验血予以证实的脑部MRI征象进行回顾性分析。结果9例脑内病变中均为多发、多部位、多种形态并存的＂三多＂征象,在艾滋病中具有较高的诊断价值,多数病灶位于大脑半球额、顶叶脑灰白质交界区（8例）,1例并发脑干病变,占位效应相对较轻,病变大多在T1WI呈等、低信号,T2WI及FLAIR序列呈高信号,增强后大部呈环状强化;7例并发脑萎缩。结论MRI在诊断艾滋病患者脑部病变方面具有较高的诊断价值。     

血清NSE变化与新生儿缺氧缺血性脑病相关性研究

目的研究新生儿窒息后发生脑损伤与血清神经元特异性烯醇化酶（NSE）动态水平变化以及与新生儿HIE的关系。方法实验组为新生儿病房Apgar评分≤3分的新生儿38例,生后观察临产表现及CT检查,结果判断组轻度HIE8例,中度17例,重度13例,并以10例正常足月新生儿做为对照,采用放射免疫分析法,检测生后1、3天天血清NSE水平。结果轻、中、重度组分别与对照组有显著差异（P〈0．01）。轻、中、重度HIE组之间3天内血清NSE比较,有显著差异（P〈0．01）。结论血清NSE水平与HIE的病情严重程度相关,可作为早期诊断中、重度新生儿缺氧缺血性脑病的客观指标。     

Changes of Cholinesterase Activities in the Rat Blood and Brain After Sarin Intoxication Pretreated with Butyrylcholinesterase

After sarin inhalation exposure of rats pretreated with equine serum butyrylcholinesterase (EqBuChE), cholinesterase activities of the whole blood, acetylcholinesterase (AChE) in erythrocytes, pontomedullar area, frontal cortex, and striatum of the brain, and plasma butyrylcholinesterase (BuChE) were determined. Using different doses of EqBuChE as a pretreatment (intraperitoneal injection), dose-dependent increases in plasma BuChE activity and no changes in the erythrocyte and brain AChE activities were demonstrated. Decreases in plasma BuChE activity and red blood cells (RBC) and brain AChE activities were observed in control rats after sarin inhalation exposure without EqBuChE pretreatment. In rats pretreated with EqBuChE, this inhibition was lower compared with control animals not only in the blood but also in the brain structures studied. These results demonstrate protective effects of EqBuChE pretreatment in rats intoxicated with sublethal concentrations of sarin by inhalation.     

Changes of cholinesterase activities in the rat blood and brain after sarin intoxication pretreated with butyrylcholinesterase

After sarin inhalation exposure of rats pretreated with equine serum butyrylcholinesterase (EqBuChE), cholinesterase activities of the whole blood, acetylcholinesterase (AChE) in erythrocytes, pontomedullar area, frontal cortex, and striatum of the brain, and plasma butyrylcholinesterase (BuChE) were determined. Using different doses of EqBuChE as a pretreatment (intraperitoneal injection), dose-dependent increases in plasma BuChE activity and no changes in the erythrocyte and brain AChE activities were demonstrated. Decreases in plasma BuChE activity and red blood cells (RBC) and brain AChE activities were observed in control rats after sarin inhalation exposure without EqBuChE pretreatment. In rats pretreated with EqBuChE, this inhibition was lower compared with control animals not only in the blood but also in the brain structures studied. These results demonstrate protective effects of EqBuChE pretreatment in rats intoxicated with sublethal concentrations of sarin by inhalation.     

Ethanol-induced hyponatremia augments brain edema after traumatic brain injury

Alcohol consumption augments brain edema by expression of brain aquaporin-4 after traumatic brain injury. However, how ethanol induces brain aquaporin-4 expression remains unclear. Aquaporin-4 can operate with some of ion channels and transporters. Therefore, we hypothesized that ethanol may affect electrolytes through regulating ion channels, leading to express aquaporin-4. To clarify the hypothesis, we examined role of AQP4 expression in ethanol-induced brain edema and changes of electrolyte levels after traumatic brain injury in the rat. In the rat traumatic brain injury model, ethanol administration reduced sodium ion concentration in blood significantly 24 hr after injury. An aquaporin-4 inhibitor recovered sodium ion concentration in blood to normal. We observed low sodium ion concentration in blood and the increase of brain aquaporin-4 in cadaver with traumatic brain injury. Therefore, ethanol increases brain edema by the increase of aquaporin-4 expression with hyponatremia after traumatic brain injury.     

Effect of a fatty-series narcotic (ether) and a barbiturate (hexenal) on the regional distribution of the total and nutritive blood flow

Inhalation of diethyl ether and intraperitoneal injection of hexenal in doses that provide a surgical state of anesthesia are accompanied by changes in the regional tone of the resistive blood vessels as well as by those in the ratio between the nutritive and shunting fractions of the blood flow in organs and tissues. The increase in the rate and enlargement of the area of transcapillary metabolism in the brain and myocardium (notwithstanding the decrease of the total blood flow in these organs) by means of the increased shunting fractions of the blood flow in vast skin and skeletal muscle areas are considered to be the most important events. Diethyl ether and hexenal cause different changes in the hepatic and renal hemodynamics.     

Acute changes in cyclic AMP levels of certain brain areas following intraventricular injection of renin in rats

Actions of the central angiotensin system on brain cAMP concentrations were studied after intraventricular injection of renin. Biosynthesis of endogenous brain angiotensin II was stimulated by 0.1 U renin and the blood pressure was elevated 40 min after the application.Stimulation of the brain angiotensin system affected cAMP metabolism in several brain areas, mostly expressed as decreased cAMP levels.Significant decreases in cAMP concentrations were found in the cerebral cortex, hippocampus, basal ganglia, various hypothalamic nuclei, substantia nigra, central grey matter and in the locus coeruleus.The unchanged cAMP levels in the nucleus of the solitary tract might indicate that intraventricular injection of renin induced an acute blood pressure elevation which is not associated with changes in the cAMP system in the primary baroreceptor area.     

Immobilization stress modifies locomotor response to catecholamine receptor agonists in rats

The effects of dopaminergic (apomorphine, nomifensine, B-HT 920) and noradrenergic (methoxamine, clonidine, salbutamol) agonists on locomotor activity were investigated in rats submitted to acute (3 h) or repeated (3 h/4 days) immobilization stress. The stress-induced functional changes were monitored by the blood level of corticosterone and the number of lymphocytes as well as the brain utilization of NA and DA. The rats subjected to acute immobilization stress displayed 30 min later an enhanced locomotor activation after apomorphine, nomifensine, or methoxamine and reduced sedative effect of clonidine, salbutamol or B-HT 920. 24 h after the repeated stress only the locomotor responses to apomorphine, nomifensine, B-HT 920 and salbutamol were modified. Spontaneous locomotor activity was not significantly changed under the influence of stressful stimuli. Increased plasma corticosterone level, strong reduction of blood lymphocytes and enhanced NA and DA utilization in the brain of rats after acute stress, together with above mentioned results, suggest that short-lasting stress evokes (30 min later) significant functional changes not only in the blood but also in the brain: enhanced CA neurons activity as well as the increased alpha 1-adrenergic and DA-post-synaptic receptors responsiveness in parallel with reduced alpha 2 - and beta-adrenergic and DA-presynaptic receptors reactivity. On the other hand, 24 h after last session of repeated stress CA brain neurons activity was not changed, however DA and beta-adrenergic responsivity was farther modified. It is postulated that the stress conditions produce in NA and/or DA brain systems a state of readiness to locomotion activating stimuli.     

Changes in brain biogenic amines and haem biosynthesis and their response to combined administration of succimers and Centella asiatica in lead poisoned rats

This study was designed to investigate the therapeutic potential of meso 2,3-dimercaptosuccinic acid (DMSA) and one of its monoesters, monoisoamyl DMSA (MiADMSA), individually or when administered in combination with an extract of Centella asiatica against experimental lead intoxication in rats. Biochemical variables indicative of alterations in the central nervous system and haem biosynthesis were investigated to determine the toxicity in male Wistar rats. Thirty five rats were exposed to 0.2% lead acetate for 10 weeks, followed by 10 days of treatment with DMSA and MiADMSA (50 mg kg(-1), i.p., once daily) alone and in combination with C. asiatica (200 mg kg(-1), p.o., once daily). Biochemical variables indicative of oxidative stress and brain biogenic amines, along with lead concentration in blood and brain, were measured. Lead exposure caused a significant depletion of blood and brain delta-aminolevulinic acid dehydratase (ALAD) activity, an important enzyme of the haem biosynthesis pathway, and glutathione (GSH) level. These changes were accompanied by a marked increase in reactive oxygen species (ROS) level, thiobarbituric acid reactive substances (TBARS), delta-aminolevulinic acid synthase (ALAS) and oxidized glutathione (GSSG) activity in blood and brain. Significant depletion of brain noradrenaline (norepinephrine, NE), 5-hydroxytryptamine (5-HT), dopamine (DA) and acetylcholinesterase (AChE) also were observed following lead exposure. Also seen was a significant depletion in brain glutathione peroxidase (GPx), glutathione S-transferase (GST) and monoamine oxidase activity, as well as blood and brain superoxide dismutase (SOD) activity. These biochemical changes were correlated with an increased uptake of lead in blood and brain. Combined administration of MiADMSA and C. asiatica was most effective in reducing these alterations, including biogenic amines, besides reducing body lead burden, compared with individual treatment with MiADMSA. Certain other biochemical variables responded favourably to combination therapy and monotherapy with MiADMSA. Thus, supplementation of C. asiatica during chelation could be recommended for achieving optimum effects of chelation therapy.     

Substantia nigra lesions attenuate the development of hypertension and behavioural hyperreactivity in spontaneously hypertensive rats

The possible relation between changes in behaviour and the development of hypertension was investigated. Depletion of striatal dopamine by lesions in the substantia nigra of Spontaneously Hypertensive Rats (SHR) was associated with an inhibition of the development of hypertension. In the open field a decrease in rearing score was found with no effect on other parameters. Rearing activity was significantly correlated with blood pressure as well as with striatal dopamine content. Blood pressure was weakly, although significantly, correlated with striatal dopamine content. Neither blood pressure nor striatal dopamine content was significantly correlated with ambulation activity. In normotensive Wistar-Kyoto rats a decrease was also found in rearing activity after nigra lesions, although this effect was less pronounced. Antihypertensive treatment of SHR with captopril or hydralazine did neither affect striatal dopamine levels nor open-field behaviour. Induction of renal hypertension or DOCA-salt hypertension in Wistar rats did not influence brain dopamine or behaviour. The results support the suggestion that brain dopamine systems may play a role in the development of hypertension in SHR as well as in the changes in behaviour observed in these rats. Changes in behaviour do not appear to be mediated by changes in blood pressure per se.     

In vivo relationships between the cerebral pharmacokinetics and pharmacodynamics of thiopentone in sheep after short-term administration

The cerebral kinetics and dynamics of thiopentone after infusions of 250, 500, and 750 mg over 2 min were examined in chronically instrumented sheep (6, 6, and 5 sheep per dose, respectively). The cerebral kinetics were studied by rapid sampling of arterial and dorsal sagittal sinus blood (afferent and efferent blood for the brain, respectively) for 40 min, and could be described by a single flow-limited compartment when arterial concentrations and cerebral blood flow were used as forcing input functions. The half-lives of equilibration between blood and the brain were estimated to be 0.67 (SEM=0.07), 0.57 (0.03) and 0.74 (0.05) min for the 250-, 500- and 750-mg doses, respectively, showing that the cerebral concentrations of thiopentone rapidly equilibrate with the afferent blood concentration. Simultaneous pharmacodynamic measurements included cerebral blood flow via a Doppler flowmeter on the sagittal sinus, and an index of the depth of anesthesia based on an algesimetry method. Thiopentone transiently reduced cerebral blood flow to 82 (SEM=3), 80% (7), and 74% (10) of baseline for the 250−, 500−, and 750-mg doses, respectively, and failure to account for drug-induced changes in cerebral bloof flow in the model overestimated the apparent volume of the brain by 12% for the 500-mg dose. For the 500-mg dose, the changes in cerebral blood flow could be accounted for by an effect compartment with a half-life of 0.82 min for arterial blood, and 0.00 min for sagittal sinus blood, showing the effluent brain concentrations were in equilibrium with this drug effect. The time course of the depth of anesthesia for the 250-mg dose could be accounted for by an effect compartment with a half-life of 1.33 min for arterial blood, and 0.41 min for sagittal sinus blood. Thus, the rate of equilibration between blood and brain could not account for all of this delay. It is concluded that after short-term administration thiopentone equilibrated rapidly with the brain, and that this is consistent with the observation that the magnitude of its clinically relevant effects closely follow the time course of the arterial blood concentrations. Supported by a grant from the National Health and Medical Research Council of Australia     

An evaluation of time-dependent changes in susceptibility of mice to pentobarbital injection

The circadian rhythm in sleep-response of mice to pentobarbital injection was studied at four different doses. Characteristics of the rhythm, determined by least squares cosine fitting, varied significantly among doses. Parallel-line bioassay of log-transformed data permitted expression of the susceptibility rhythm as a variation in relative potency.Concomitant study of circadian-rhythmic and age-related changes in sleep-response to pentobarbital injection indicated significant differences on both time scales, and the absence of interaction.At circadian phases of long and short sleep duration, brain and blood pentobarbital concentrations were determined at intervals after injection, up to and including the time of awakening. The waking concentrations in brain and blood were significantly higher at the circadian phase of short sleep duration, while time-dependent differences in the rate of barbiturate disappearance from these sites could not be demonstrated. The waking brain pentobarbital concentration at a given circadian phase also differed between 4-month and 9-month old mice.Factors possibly responsible for time-dependent changes in susceptibility to barbiturate injection are discussed.     

引起重型颅脑外伤后继发性脑损伤相关因素的临床研究

目的探讨引起重型颅脑损伤继发性脑损伤的相关因素。方法回顾性分析患者住院病历;比较死亡组与存活组在白细胞计数、体温、早期血压、血糖、血钠等因素上差异。结果120例重型颅脑损伤中死亡42例,病死率为35.0%;继发性脑损伤的因素有关包括白细胞≥20.0×109/L、体温≥39.0℃、血糖≥11.1mol/L、血钠≥145mmol/L、血压≤90/60mmHg等(P<0.05)。结论重型颅脑损伤患者病死率高,影响因素复杂,高热、低血压、电解质紊乱、白细胞增高均属于继发性脑损伤指标,都直接参与了颅脑伤的继发性病理损害。高度重视监测和严格控制这些继发性脑损伤指标的变化,对提高颅脑伤救治水平有重要意义。     

大鼠脑缺血再灌注后血脑屏障超微结构的改变

目的：研究大鼠脑缺血再灌注后电镜超微结构血脑屏障的特异改变。方法：采用线栓法制成大鼠大脑中动脉闭塞（MCAO）局灶性缺血2h再灌注24h模型。利用电镜技术研究脑缺血再灌注后电镜超微结构血脑屏障的特异改变。结果：在脑微血管内皮细胞核固缩，内皮细胞连接间隙和通透性增加，有的可见连接内皮细胞的基质和基膜的完整性缺失，微血管周围胶质细胞的伪足肿胀、进行性退变，微血管腔狭窄。白毛细血管内皮细胞向管腔内伸出许多突起。结论：局灶性脑缺血再灌注后24h血脑屏障的超微结构改变，可能对血液和神经元之间的营养传递有益。这可能是代偿修复和血管再生的机制之一。     

A comparison of the effects of chronic administration of ethanol and acetaldehyde to mice: evidence for a role of acetaldehyde in ethanol dependence

After chronic exposure to ethanol or acetaldehyde vapour in concentrations which depress locomotor activity, mice show similar behavioural changes during withdrawal, and there is some degree of cross dependence. Mice exposed to acetaldehyde vapour had blood acetaldehyde concentrations similar to those of ethanol-treated mice, but brain acetaldehyde concentrations were apparently lower. There was no accumulation of acetaldehyde in blood or brain in either group during chronic administration. Chronic ethanol or acetaldehyde administration to mice is associated with an increase in the concentrations of the brain monoamines noradrenaline, dopamine and 5-HT. Withdrawal of ethanol or acetaldehyde is associated with a further, rapid, transient rise in the brain catecholamines, noradrenaline and dopamine. These results suggest that acetaldehyde may play a role in some of the biochemical and behavioural changes associated with ethanol dependence.     

血神经元特异性烯醇化酶与远期神经系统发育障碍的关系

目的 探讨脑损伤患儿血中神经元特异性烯醇化酶变化与远期神经系统发育障碍的相关性,以期对新生儿脑损伤预后及时预报,为早期干预提供理论依据.方法 选择40例围生期脑损伤新生儿为研究对象,同时选择20例同期出生的健康新生儿为对照组,两组均于生后72 h进行检测血浆神经元特异性烯醇化酶,并对两组定期追踪发育情况,以盖塞尔量表评价.经统计学处理分析神经元特异性烯醇化酶与围生期脑损伤患儿远期神经系统发育障碍的相关性.结果 脑损伤组血神经元特异性烯醇化酶浓度为(20.5±6.9)μg/L,明显高于健康对照组的(7.8±3.8)μg/L(t=4.85,P＜0.01);脑损伤组15月龄盖塞尔量表评价发育商可疑组生后3 d血神经元特异性烯醇化酶浓度为(17.6±5.1)μg/L,明显高于发育商正常组的(12.07±1.86)μg/L(t=3.73,P＜0.01),发育商异常组生后3 d血神经元特异性烯醇化酶浓度为(27±7.4)μg/L,明显高于发育商正常组的(12.07±1.86)μg/L(t=3.94,P＜0.01).结论 神经元特异性烯醇化酶变化可作为早期诊断围生儿脑损伤的主要指标以及远期预后指标.     

Glucose protects DBA/2J mice from audiogenic seizures: Correlation with brain glycogen levels

The time courses of changes in liver, blood, and brain cortical glucose and glycogen levels were measured in 21-day-old DBA/2J mice after an IP injection of 10 g/kg glucose. Other mice were injected with glucose and tested for susceptibility to audiogenic seizures (AGS). Susceptibility to AGS fell from maximal levels to complete protection by 4 h, remained low through 6 h, then began to return to control levels by 8 h. Liver, blood, and brain glucose levels all rose to a peak soon after the injection, then fell linearly and returned to control levels by 6–8 h. Changes in brain glycogen levels reflected changes in AGS susceptibility.