川芎嗪对发育期大鼠惊厥性脑损伤海马ATP酶与脑含水量变化的影响

目的观察发育期大鼠反复惊厥后海马ATP酶与脑含水量的动态变化及川芎嗪干预对其的影响。方法162只20日龄健康sD大鼠随机分为3组：对照组、惊厥组及川芎嗪干预组。通过三氟乙醚反复吸入（连续6次，每天1次）制作发育期大鼠惊厥动物模型。取海马组织匀浆，检测各组动物反复惊厥后6h、1d、3d、7d海马组织中Na^＋-K^＋-ATP酶、Ca2^＋-ATP酶的活性变化，同时观察脑含水量变化和光镜下海马区神经元病理改变。结果反复惊厥后6h、1d、3d海马Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶的活性均较对照组显著降低（P＜0．01），伴随脑含水量显著升高（P＜0．01），第7天三者与对照组相比较差异均无统计学意义（P＞0、05）。脑含水量变化与海马Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶的活性变化均呈显著负相关（前者r=-0．711，后者r=-0．673，P均＜0．01）。川芎嗪干预组海马神经元水肿、变性坏死明显减轻，各时间点Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶的活性较惊厥组显著升高（P＜0．05或P＜0、01），脑含水量显著降低（P＜0．01）。结论Na^＋K^＋ATP酶、Ca^2＋-ATP酶的活性降低与惊厥性脑水肿和海马神经元迟发性损害密切相关，川芎嗪对发育期惊厥性脑损伤的保护作用可能与提高海马Na^＋-K^＋-ATP酶、Ca^2＋-ATP酶的活性有关。     

经侧脑室对创伤性脑损伤进行亚低温治疗的疗效观察

目的采用经侧脑室灌注25℃林格氏液的方法对实验动物创伤性脑损伤进行亚低温治疗，观察其疗效并初步探讨相关治疗机制。方法共选取21只新西兰兔，将其随机分为对照组、颅脑外伤组及亚低温组。颅脑外伤组及亚低温组选用重物自由落体撞击方式制作脑损伤模型，对亚低温组实验动物脑损伤部位给予亚低温干预（经侧脑室灌流25℃林格氏液）。待治疗结束后提取各组实验动物损伤灶脑组织，分别检测其水、Na^＋、K^＋含量，同时观察神经细胞病理形态学改变情况。结果颅脑外伤组与亚低温组神经元损伤数量均明显多于对照组（P〈0．01），但亚低温组神经元损伤数量显著少于颅脑外伤组（P〈0．01）；颅脑外伤组与亚低温组脑组织水分、Na^＋含量均较对照组明显增多（P〈0．01），但亚低温组水分、Na^＋含量均显著低于颅脑外伤组（P〈0．01）；颅脑外伤组与亚低温组脑组织K^＋含量均较对照组明显减少（P〈0．01），但亚低温组K^＋含量显著高于颅脑外伤组（P〈0．01）。结论经侧脑室灌流25℃林格氏液进行亚低温干预对实验动物创伤性脑损伤具有显著疗效，能减轻脑水肿，抑制神经细胞损伤。     

7-硝基吲唑对大鼠创伤性脑损伤早期脑水肿的影响

目的：探讨神经元型一氧化氮合酶（nNOS）在创伤性脑损伤（TBI）中的作用。方法：采用落体法大鼠TBI动物模型，观察特异性nNOS抑制剂7-硝基吲唑（7-NI）对TBI早期脑水肿和病理变化的影响。结果：与伤后6h组相比，7-NI能显著减少脑组织含水量和脑组织中Na^＋的含量（P值均〈0．05），而增加K^＋的含量（P〈0．05）．并能改善脑创伤后的病理变化。7-NI的作用可被L-精氨酸逆转．D-精氨酸无效。结论：nNOS来源的一氧化氮对TBI早期起毒性作用，nNOS抑制剂有可能成为治疗继发性脑损伤的新途径。     

传统方剂五苓散加减后2种复方制剂对细胞毒性脑水肿的作用

目的：观察在传统方剂五苓散的基础上加用田七、丹参等组成制剂健神利水Ⅰ号与加用石菖蒲、夏枯草等组成的制剂醒脑消肿胶囊治疗脑出血细胞毒性脑水肿的效果差异，并分析引起差异的原因。 方法：①实验于2001-05／06在广西中医学院第一附属医院中心实验室完成。选用出生6个月的新西兰大耳白兔32只，雌雄不拘。②先用区组随机法将动物分为4组：空白对照组（未造模，只灌胃温水），模型组，健神利水Ⅰ号组和醒脑消肿胶囊组，每组8只；再将每组分为造模后12和24h2个时间点进行观察，每时间点4只动物。健神利水Ⅰ号水煎剂由三七15g，丹参15g，茯苓10g，猪苓10g，泽泻10g，白术10g，桂枝10g组成。由广西中医学院第一附属医院药房提供，用韩国产煎药机煎成200mL药液，真空密封袋4℃保存。醒脑消肿胶囊：批准文号南药（96）05079，由夏枯草15g，石菖蒲15g，茯苓10g，猪苓10g，泽泻10g，白术10g，桂枝10g组成，含生药13．33s／粒；由广西中医学院第一附属医院制剂室提供；用温水制成混悬液。2种中药给药量均为l1．5mL／kg，于实验前30min经胃管注入，其余各组以温水11．5mL／kg，于实验前30min经胃管注入，每组干预12及24h后以空气栓塞法处死动物。③采用全脑重／体质量&;#215;100％的公式计算脑系数；（湿重-干重）／湿重&;#215;100％的公式计算脑含水量；ATP酶试剂盒定磷法测定A11P酶含量；火焰光度法测定K^＋，Na^＋含量；邻一甲酚酞络合酮比色法测定Ca^2＋含量。④正态性检验用矩法，组间比较用F检验，组间两两比较用q检验，时间段（同组）内比较用t检验，方差不齐用秩和检验。 结果：兔32只均进入结果分析。①两用药组兔脑系数与脑含水量均明显低于模型组（P〈0．01），其中健神利水Ⅰ号组兔脑系数与脑含水量明显低于醒脑消肿胶囊组（P〈0．05）。②模型组造模后12，24h兔左侧颢叶脑组织Na^2＋含量明显高于两用药组（P〈0、01），健神利水Ⅰ号组明显低于醒脑消肿胶囊组（P〈0．05）；模型组造模后24h兔左侧颢叶脑组织Na^＋ -K^＋ -ATP酶活力明显低于假手术组和两用药组（P〈0．01），健神利水Ⅰ号组明显高于醒脑消肿胶囊组（P〈0．05）。模型组造模后24h兔左侧颢叶脑组织K^＋含量明显低于假手术组（P〈0．01）。③各组兔左侧额叶脑组织Ca^2＋含量和Ca^2＋ -ATP）酶活力在造模后12，24h差异不明显（P〉0．05）。 结论：健神利水Ⅰ号对脑细胞的保护和脱水作用要强于醒脑消肿胶囊，可能与其提升Na^＋ -K^＋ -ATP酶含量有关。     

心房肽及血管紧张素Ⅱ在家兔内毒素性脑水肿中的变化

目的：探讨内毒素性脑水肿心房肽（ANP）和血管紧张素Ⅱ（ANGⅡ）的变化及其意义。方法：30只新西兰白兔，分内毒素组（25只）和对照组（5只），内毒素组于每只兔脑池内注射内毒素400μg，对照组注入等量生理盐水。于不同时间收集血液、脑脊液和脑组织，用放射免疫法测定ANP和ANGⅡ含量，干燥法测定脑组织含水量。结果：注射内毒素6h后，脑组织（海马区）、脑脊液和血浆中ANP和ANGⅡ含量显著高于对照组和注射前（P＜0．05或P＜0．01），12h后脑组织和脑脊液ANP逐渐降低，24h后明显低于对照组，而ANGⅡ仍然持续增高。脑组织含水量明显高于对照组（P＜0．05或P＜0．01），24h后脑含水量达到高峰。结论：中枢神经系统在内毒素作用下，中枢和周围组织ANP／ANGⅡ平衡失调，早期ANP升高可能是代偿性机制，持续性ANGⅡ增高可加剧脑水肿和炎症损害。     

大承气汤对家猫脑出血性期的保护作用及一氧化氮改变的研究

目的：探讨大承气汤对家猫脑出血脑保护作用机制,方法：采用家猫脑出血模型,观察脑出血后及药物作用后1．5,12h脑组织中一氧化氮（NO）含量及Na^ K^ -ATP酶活性变化。结果：药物作用后12h脑吕NO含量,及Na^ K^ －ATP酶活性变化,与模型组比较有显著差异,（P＜0．05）,结论：大承气汤可降低NO的毒性,增加Na^ K^ -ATP酶的活性,对出血脑组织有保护作用。     

星状神经节阻滞对家兔脑缺血再灌注时氧自由基损伤的保护作用

目的：研究星状神经节阻滞（SGB）对脑缺血再灌注家兔脑组织超氧化物歧化酶（SOD）、丙二醛（MDA）以及含水率的影响．以探讨其对氧自由基损伤的作用机制。方法：选择SGB模型有效的家兔32只，随机分为4组（n=8）：假手术组（Sham组）、空白对照组（I／R组）、生理盐水对照组（NS组）和SGB组。SGB组再灌注开始时从兔颈部导管注人0．25％丁哌卡因0．5ml／h至再灌注12h时。NS组则注入NS0．5ml／h。I／R组不用任何药。各组于再灌注12h时断头取脑制成10％脑组织匀浆，检测SOD活性、MDA含量。结果：与Sham组比较，I／R组、NS组SOD活性均明显降低（P〈0．01），MDA含量明显增加（P〈0．01），脑组织含水率增加（P〈0.05），而I／R组与NS组比较差异无显著性意义；与I／R组、NS组比较，SGB组SOD活性显著升高而MDA含量明显降低（p〈0．01），脑组织含水率下降（P〈0．05）。结论：SGB可明显减轻脑水肿，提高脑组织内源性SOD生物活性，降低MDA含量，具有明显的抗氧自由基损伤作用，并因此而起到抗脑缺血再灌注损伤的作用。     

神经肽Y在家兔内毒素性脑损伤模型中的时相变化

目的：探讨家兔内毒素性脑损伤模型中脑组织、脑脊液（CSF）、和血浆神经肽Y（NPY）的时相变化及与病情的关系。方法：35只新西兰白兔，随机分内毒素组（30只）和对照组（5只），内毒素组于每兔脑池内注射内毒素100μg/kg体重，对照组注入等容量生理盐水。于注射内毒素后3h、6h、12h、24h、48h、72h收集血浆、CSF，并处死家兔留取脑组织（海马区），应用放射免疫法测定NPY含量，干燥法测定脑组织含水量。结果：注射内毒素后，脑组织、CSF和血浆中NPY含量显著高于对照组和注射前（P＜0．05或P＜0．01），24h为高峰，分别为23．7ng/g、783．7ng/L和821．7ng/L；脑组织含水量明显高于对照组（P＜0．05或P＜0．01），24h脑含水量达到高峰。结论：内毒素诱导家兔脑水肿情况下，中枢神经系统和外周神经组织存在NPY的异常产生和释放，与炎症损害有关。     

左旋四氢巴马汀在大鼠全脑缺血-再灌流时对脑组织电解质含量的影响

目的：通过观察脑缺血－再灌流时脑组织钙、镁、锌、钠、铁含量的变化，探讨左旋四氢巴马汀在全脑缺血－再灌流损伤时的作用机制。方法：建立大鼠急性脑缺血－再灌流损伤模型，用原子分光光度仪检测脑组织电解质含量。结果：与假手术组比较脑缺血－再灌流12h组钙、锌、钠、钾含量增高（P＜0．01），铁含量亦增高（P＜0．05），镁含量降低（P＜0．01）；24h钙、锌、钠含量进一步增高（P＜0．01），镁含量进一步降低（P＜0．01），钾和铁含量与假手术组接近（P＞0．05）。左旋四氢巴马汀在脑缺血再灌流12h和24h均能抑制脑组织钙（P＜0．01）、锌（P＜0．01）、钠（P＜0．05，P＜0．01）含量的上升，并提高脑组织镁（P＜0．01）和钾（P＜0．05，P＜0．01）的含量，降低铁含量（P＜0．05，P＜0．01）。结论：左旋四氢巴马汀可抑制脑缺血－再灌流期间脑组织钙、锌、钠含量的上升并提高镁和钾含量，降低铁含量。     

窒息对新生大鼠脑组织含水量及IL-1β影响的实验研究

目的：探讨窒息后新生大鼠脑组织含水量和IL－1β在不同时相的变化，进一步完善缺氧缺血性脑病（HIE）发生发展的机制，方法：建立新6生大鼠窒息模型，观察窒息后不同时相脑组织水分和IL－1β的变化，并与对照组比较。结果：窒息组脑组织含水量明显高于对照组（P＜0．05），脑组织IL－1β极明显增加（P＜0．01），其改变以24h后最为明显。结论：窒息可致脑水肿，是发生HIE的重要因素。IL－β参与HIE的发病过程，其含量变化有助于判断HIE病变程度和病情进展。     

Imaging brain development: the adolescent brain

The past 15 years have seen a rapid expansion in the number of studies using neuroimaging techniques to investigate maturational changes in the human brain. In this paper, I review MRI studies on structural changes in the developing brain, and fMRI studies on functional changes in the social brain during adolescence. Both MRI and fMRI studies point to adolescence as a period of continued neural development. In the final section, I discuss a number of areas of research that are just beginning and may be the subject of developmental neuroimaging in the next twenty years. Future studies might focus on complex questions including the development of functional connectivity; how gender and puberty influence adolescent brain development; the effects of genes, environment and culture on the adolescent brain; development of the atypical adolescent brain; and implications for policy of the study of the adolescent brain.     

Mediators of brain edema and secondary brain damage

Progress is our understanding of the roles of vasogenic and cytotoxic brain edema in secondary brain damage can be expected from studies of the ability of biochemical factors to open the blood-brain barrier, derange the microcirculation, and cause cell swelling and necrosis. Mediator compounds are considered to form or to become released in an area of primarily damaged brain (necrosis) and to enter the cerebral parenchyma through the broken blood-brain barrier from the intravascular space. Many biochemical factors must be considered. We suggested three criteria for determining the roles of mediators: a) they must inflict brain tissue damage, b) they must occur in pathologic concentrations or in compartments not normally present, and c) specific inhibition should attenuate secondary brain damage. These requirements are met by the kallikrein-kinin system and by glutamate. In the case of arachidonic acid and its many metabolites, the concept is difficult to test because fatty acids may be active only if not bound to proteins, and therapeutic inhibition might be difficult. A variety of mediators may enhance each other in a cascade manner by various initiating reactions that might be amenable for pharmacologic inhibition.     

Hypoglycemia, functional brain failure, and brain death

Hypoglycemia commonly causes brain fuel deprivation, resulting in functional brain failure, which can be corrected by raising plasma glucose concentrations. Rarely, profound hypoglycemia causes brain death that is not the result of fuel deprivation per se. In this issue of the JCI, Suh and colleagues use cell culture and in vivo rodent studies of glucose deprivation and marked hypoglycemia and provide evidence that hypoglycemic brain neuronal death is in fact increased by neuronal NADPH oxidase activation during glucose reperfusion (see the related article beginning on page 910). This finding suggests that, at least in the setting of profound hypoglycemia, therapeutic hyperglycemia should be avoided.     

Anemia and brain oxygen after severe traumatic brain injury

Purpose

To investigate the relationship between hemoglobin (Hgb) and brain tissue oxygen tension (PbtO₂) after severe traumatic brain injury (TBI) and to examine its impact on outcome.

Methods

This was a retrospective analysis of a prospective cohort of severe TBI patients whose PbtO₂ was monitored. The relationship between Hgb—categorized into four quartiles (≤9; 9–10; 10.1–11; >11?g/dl)—and PbtO₂ was analyzed using mixed-effects models. Anemia with compromised PbtO₂ was defined as episodes of Hgb?≤?9?g/dl with simultaneous PbtO₂?Results We analyzed 474 simultaneous Hgb and PbtO₂ samples from 80 patients (mean age 44?±?20?years, median GCS 4 (3–7)). Using Hgb?>?11?g/dl as the reference level, and controlling for important physiologic covariates (CPP, PaO₂, PaCO₂), Hgb?≤?9?g/dl was the only Hgb level that was associated with lower PbtO₂ (coefficient ?6.53 (95?% CI ?9.13; ?3.94), p?2?p?=?0.008), controlling for age, GCS, Marshall CT grade, and APACHE II score.

Conclusions

In this cohort of severe TBI patients whose PbtO₂ was monitored, a Hgb level no greater than 9?g/dl was associated with compromised PbtO₂. Anemia with simultaneous compromised PbtO₂, but not anemia alone, was a risk factor for unfavorable outcome, irrespective of injury severity.     

Effect of brain cooling on brain ischemia and damage markers after fluid percussion brain injury in rats

Although systemic cooling had recently been reported as effective in improving the neurological outcome after traumatic brain injury, several problems are associated with whole-body cooling. The present study was conducted to test the effectiveness of brain cooling without interference with the core temperature in rats after fluid percussion traumatic brain injury (TBI). Brain dialysates ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and injury (e.g., glycerol) markers before and after TBI were measured in rats with mild brain cooling (33 degrees C) and in the sham control group. Brain cooling was accomplished by infusion of 5 mL cold saline via the external jugular vein under general anesthesia. The weight loss was determined by the difference between the first and third day of body weight after TBI. The maximum grip angle in an inclined plane was measured to determine motor performance, whereas the percentage of maximal possible effect was used to measure blockade of proprioception. The triphenyltetrazolium chloride staining procedures were used for cerebral infarction assay. As compared with those of the sham-operated controls, the animals with TBI had higher values of extracellular levels of glutamate, lactate-to-pyruvate ratio, and glycerol in brain and intracranial pressure, but lower values of cerebral perfusion pressure. Brain cooling adopted immediately after TBI significantly attenuated the TBI-induced increased cerebral ischemia and injury markers, intracranial hypertension, and cerebral hypoperfusion. In addition, the TBI-induced cerebral infarction, motor and proprioception deficits, and body weight loss evaluated 3 days after TBI were significantly attenuated by brain cooling. We successfully demonstrate that brain cooling causes attenuation of TBI in rats by reducing cerebral ischemia and injury resulting from intracranial hypertension and cerebral hypoperfusion. Because jugular venipuncture is an easy procedure frequently used in the emergency department, for preservation of brain function, jugular infusion of cold saline may be useful in resuscitation for trauma patients.     

Enhanced brain extraction improves the accuracy of brain atrophy estimation

BET (Brain Extraction Tool) is a widely used computer program to automatically separate brain from non-brain structures in MR images. This procedure is used in SIENAX and SIENA, which are robust approaches to quantifying brain volume (atrophy state) and volume change (atrophy rate), respectively. Occasionally, however, BET produces imperfect results (e.g., inclusion of non-brain structures). This is usually either ignored (if inaccuracies are small) or corrected by manual adjustment, with the disadvantages of user intervention. We describe here a new, automated option in BET. This is based on the original BET, but uses standard-space masking to remove tissue around the eyes, and further morphological operations and thresholding to refine eyeball removal and eliminate additional non-brain tissues. To assess whether the new BET procedure improves brain volume measurements, this was compared with the traditional and manual editing procedures in SIENA and SIENAX. Measures of atrophy rate and state were significantly higher with the traditional procedure than with the manual editing and new procedures. In contrast, both atrophy measures were almost identical and highly correlated when the manual editing and new procedures were used. The voxels excluded with these two procedures showed close overlap, as judged by the Dice overlap coefficient. We conclude that, in SIENA and SIENAX, the proposed BET procedure shows results matching those obtained after manual editing, thus more closely approximating the "true" brain volume. Multicentre studies monitoring brain atrophy in clinical trials may receive benefit by using this unbiased, fully automated procedure.