急性颅脑损伤后脑脊液抑制性氨基酸的变化及意义

目的探讨脑脊液中抑制性氨基酸的水平与颅脑损伤严重程度的关系。方法将71例急性颅脑损伤患者按入院时GCS评分分为9~15分组（37例）和3~8分组（34例）,伤后1、3、7 d采集脑脊液标本;以28例正常脑脊液标本作对照组。采用柱前衍生反相高效液相色谱紫外吸收检测法定量分析脑脊液标本中γ-氨基丁酸（GABA）、牛磺酸（Tau）和丙氨酸（Ala）浓度。结果颅脑损伤后脑脊液GABA、Tau浓度均高于对照组,GCS 3~8分组Tau浓度均明显高于GCS 9~15分组（P〈0.05）。颅脑损伤后1、7d,GCS 3~8分组GABA浓度高于GCS 9~15分组（P〈0.05）,伤后3 d时两组浓度无显著性差异（P〉0.05）。颅脑损伤后Ala浓度较对照组明显下降（P〈0.05）。结论脑脊液GABA、Tau在颅脑损伤后反应性增高提示其可能与颅脑损伤的严重程度相关。脑脊液Ala浓度在颅脑损伤后下降提示颅脑损伤后部分脑保护机制受到损害。     

重型颅脑损伤患者脑脊液SBDPs的水平变化

目的探讨重型颅脑损伤患者脑脊液中αⅡ血影蛋白裂解产物（SBDPs,包括SBDP140和SBDP120）浓度与颅脑损伤的程度和患者预后的关系。方法选择40例重型颅脑损伤（Gcs≤8分）患者（颅脑损伤组）,伤后6h、12h、24h、1d、2d、3d、4d、5d．6d．7d取脑脊液采用酶联免疫吸附法检测SBDP140和SBDP120浓度;选择24例脑积水患者作为对照组。结果不同时间点颅脑损伤组脑脊液SBDP145和SBDP120浓度均明显高于对照组（P〈0.05）,SBDP145在伤后6h就达最高峰,而SBDP120直到到伤后5d才达峰值。不同时间点伤后3个月死亡的颅脑损伤患者脑脊液的SBDP145和SBDP120浓度明显高于生存的患者（p〈0．05）。入院时GCS评分6—8分患者脑脊液离脊液SBDP145的浓度明显低于入院时GCS评分3-5的患者（P〈0．05）,而SBDP120的浓度两者之间无明显变化（P〉0．05）。结论颅脑损伤患者脑脊液SBDPs与颅脑损伤的严重性和患者预后有关。     

脑梗塞患者脑脊液兴奋性氨基酸含量的测定及其意义

采用高效液相色谱法检测46例脑梗塞患者和30例正常对照者脑脊液中兴奋性氨基酸递质谷氨酸（Glu）、天门冬氨酸（Asp）水平及抑制性神经递质γ-氨基丁酸（GABA）含量．结果表明脑梗塞发生12小时至4天脑脊液中谷氨酸、天门冬氨酸显著升高，恢复期降至正常水平；γ-氨基丁酸在脑梗塞急性期也升高，恢复期下降；证明谷氨酸、天门冬氨酸在神经元缺血损伤中起重要作用。急性脑梗塞患者脑脊液兴奋性和抑制性氨基酸递质可作为一个敏感指标，早期诊断脑缺血的发生，推测脑梗塞的严重程度，具有重要的临床意义。     

精神病患者脑立体定向术前后脑脊液中单胺类递质的变化

对16例精神病患者作了脑立体定向手术,靶点选择双扣带回、杏仁核、内囊前肢,发现术后疗效好的患者脑脊液中去甲肾上腺素含量减低,多巴胺含量升高;疗效差者脑脊液中多巴胺和去甲肾上腺素含量变化不大,提示该治疗的机理可能与中枢神经内单胺递质改变有关。     

颅脑外伤后血清、脑脊液髓鞘碱性蛋白的变化及其临床意义

目的①探讨颅脑外伤后血清、脑脊液髓鞘碱性蛋白（MBP）的变化及其意义；②探讨血清、脑脊液MBP水平与伤情、CT、颅内压（ICP）、脑灌注压（CCP）的关系。方法采用免疫组化法测定90例颅脑损伤病人伤后24h内、3d、7d时的血清、脑脊液MBP水平，并结合颅脑损伤程度、CT、ICP、CPP进行分析。结果①颅脑损伤病人血清、脑脊液MBP浓度升高的程度与脑损伤程度密切相关；②血浆、脑脊液MBP水平随ICP增加而升高，随CPP增高而降低；③血清、脑脊液MBP水平随CT图像改变而变化。结论监测血清、脑脊液MBP浓度，联合CT、ICP、CPP等指标，可更准确地判断病情。     

脑梗塞患者脑脊液兴奋性氨基酸含量的测定及其意义

采用高效液相色谱法检测46例脑梗塞患者和30例正常对照者脑脊液中兴奋性氨基酸递质谷氨酸(Glu)、天门冬氨酸(Asp)水平及抑制性神经递质γ-氨基丁酸(GABA)含量。结果表明脑梗塞发生12小时至4天脑脊液中谷氨酸、天门冬氨酸显著升高,恢复期降至正常水平;γ-氨基丁酸在脑梗塞急性期也升高,恢复期下降;证明谷氨酸、天门冬氨酸在神经元缺血损伤中起重要作用。急性脑梗塞患者脑脊液兴奋性和抑制性氨基酸递质可作为一个敏感指标,早期诊断脑缺血的发生,推测脑梗塞的严重程度,具有重要的临床意义。     

抑郁症与血浆中单胺类神经递质代谢产物

目的 检测抑郁症患血浆中单胺递质代谢产物在抗抑郁治疗前后的差异，探讨抑郁症及抗抑郁治疗与血浆中单胺递质代谢产物浓度的相关性。方法 用高效液相色谱法对40例抑郁症患治疗前后血浆中单胺递质代谢产物的浓度进行测定，用汉密尔顿抑郁量表评定抑郁症患的临床疗效。结果 抑郁症患血浆中单胺递质代谢产物5－HIAA、MHPG、HVA的浓度均显低于正常对照组，P＜0．05。经过4周住院治疗显效，HAMD分显下降，患血浆中5－HIAA、MHPG含量与治疗前比较明显升高，有显差异，P＜0．05；但HVA没有明显变化。结论 外周的单胺递质代谢产物可反映脑中单胺类神经递质的状态，血浆中单胺递质的变化可作为抑郁症及疗效评定的一个重要参考指标。     

颅脑损伤后病人血清皮质醇的变化规律

目的研究颅脑损伤后病人体内血清皮质醇变化与预后之间的关系。方法 140例颅脑损伤病人（轻型26例、中型34例、重型64例和特重型16例）在伤后1 d、2 d、3 d、5 d、7 d和14 d早上7：00连续测定血清皮质醇,并进行分析研究,探讨颅脑损伤病人血清皮质醇的变化规律。结果血清皮质醇水平出现波动的病例数在轻型组、中型组、重型组和特重型分别为1例（3.9%）、23例（67.7%）、48例（75.0%）和12例（75.0%）。各组皮质醇波动幅度,在伤后3 d内差别较大,而3 d后基本降至正常范围。病人伤后血清皮质醇下降者预后差,伤后血清皮质醇上升者和正常范围内波动者预后较好。结论颅脑损伤病人伤后血清皮质醇变化与颅脑创伤程度以及病人年龄呈正相关,伤后血清皮质醇下降者预后最差。     

重型颅脑损伤患者外周血内皮祖细胞动态变化及意义

目的探讨重型颅脑损伤患者外周血内皮祖细胞（EPCs）水平的动态变化及其意义。方法收集我院收治的重型颅脑损伤患者58例（颅脑损伤组）、健康体检者22例（对照组）,采用流式细胞技术检测颅脑损伤组患者伤后1、4．7、14、21d及对照组外周血EPCs水平。结果与对照组相比,伤后1d,颅脑损伤组外周血EPCs水平无显著变化（P〉0．05）,伤后4d降至最低值（P〈0．05）;随后逐渐升高,伤后7d达最高峰（P〈0.05）,随后逐渐下降,伤后21d与对照组无显著差异（P〉0．05）。伤后1d外周血EPCs水平与入院时患者GCS评分呈正相关（RS=0．452,P〈0．05）;伤后7、14、21d外周血EPCs水平与伤后6个月GOS评分呈正相关（rs分别为0．423,0．469,0．455;P〈0．05）。结论外周血EPCs可作为重型颅脑损伤患者预后的一个重要评价指标。     

急性颅脑损伤后垂体激素变化规律探讨

目的：探讨急性颅脑损伤患者垂体激素水平的变化及与颅脑损伤程度的相关性。方法随机抽取60例颅脑损伤患者作为观察组（损伤程度采用GCS评分评估）,15例志愿者为对照组,采用酶联免疫定量分析法检测伤后1、3、7、30d血清催乳素（PRL）、卵泡刺激素（FSH）、黄体生成激素（LH）和促甲状腺激素（TSH）水平。结果观察组伤后血清PRL、FSH、LH显著升高（P＜0.05）,TSH略降低（P＞0.05）;观察组血清PRL、FSH、LH水平早期升高明显（72h内尤为明显）,后逐渐降低。颅脑损伤越重,PRL、FSH、LH值早期越高。结论急性颅脑损伤垂体激素PRL、FSH及LH水平于伤后早期明显升高,TSH稍降低,变化程度与颅脑损伤严重程度有关。     

Mild closed head traumatic brain injury-induced changes in monoamine neurotransmitters in the trigeminal subnuclei of a rat model: mechanisms underlying orofacial allodynias and headache

Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias, a hypersensitive pain response induced by non-painful stimulation. These allodynias, tested using thermal hyperalgesia, correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway, espe-cially in the trigeminal nucleus caudalis. This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis, pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury, which are related to tactile allodynia, touch-pressure sensitivity, and visceral pain. Our results exhib-ited significant alterations in the excitatory monoamine, serotonin, in spinal trigeminal nucleus oralis and pars interpolaris which usually modulate tactile and mechanical sensitivity in addition to the thermal sensi-tivity. Moreover, we also detected a robust alteration in the expression of serotonin, and inhibitory molecule norepinephrine in the nucleus tractus solitaries, which might indicate the possibility of an alteration in visceral pain, and existence of other morbidities related to solitary nucleus dysfunction in this rodent model of mild to moderate closed head traumatic brain injury. Collectively, widespread changes in monoamine neurotransmitter may be related to orofacial allodynhias and headache after traumatic brain injury.     

损伤性窒息犬大脑皮质运动区单胺类递质的变化

目的 探讨损伤性窒息犬大脑皮质运动区单胺类递质的变化,为其治疗提供科学依据。方法 建立犬损伤性窒息脑损害模型,用高效液相电化学方法（ＨＰＬＣ－ＤＣ）测定大脑皮质中单胺类递质及其代谢产物在不同时间的改变。结果 大脑皮质运动区在损伤后２小时５－羟吲哚乙酸（５－ＨＩＡＡ）明显升高;８小时后５－羟色胺（５－ＨＴ）、高香草酸（ＨＶＡ）升高;去甲肾上腺素（ＮＥ）及３、４－双羟苯乙酸（ＤＯＰＡＣ）变化不明显。结论 单胺类神经递质参与了损伤性窒息后继发脑损害的病理过程,早期应用５－羟色胺拮抗剂或合成抑制剂是治疗损伤性窒息脑损害的一个可行方法。     

早期血容量的维持对重型原发性脑干损伤预后的影响

目的探讨早期血容量的维持对重型原发性脑干损伤患者预后的影响。方法对21例重型原发性脑干损伤患者伤后采用常规治疗的同时,早期给予大剂量胶体液以维持足够的血容量,评价患者疗效。结果伤后3个月进行GOS评分:良好8例,轻残2例,重残4例,植物生存4例,死亡3例。结论早期血容量的维持可降低重型原发性脑干损伤的死亡率、致残率,改善预后。     

Monoamine neurotransmitter interactions and the prediction of antidepressant response

Clinical studies of monoamine neurotransmitter function in depression have concentrated on individual monoamines without focusing on interactions between monoamine systems. Virtually all modern studies have found significant correlations between monoamine metabolite concentrations in cerebrospinal fluid (CSF). These correlations should in part reflect interactions between central monoamine systems. In the present analysis, CSF had been obtained from depressed patients before (n = 40) and after (n = 36) antidepressant treatment. The patients were grouped based on their response to treatment. Absolute concentrations of CSF monoamine metabolites (homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethyleneglycol) did not differ between the two groups before or after treatment. However, when correlations between metabolites were compared, nonresponders to treatment differed considerably from responders. In responders, as in previously described normal populations, all three metabolites correlated with one another before and after treatment, and treatment-induced changes in metabolite concentrations also correlated with one another. In contrast, metabolites in nonresponders did not correlate with one another before treatment, nor did treatment-induced changes correlate with one another in this group. Furthermore, correlations between treatment-induced changes in metabolites differed significantly between responders and nonresponders, and there was a trend for pretreatment correlations to differ as well. The lack of correlation between monoamine metabolites in nonresponders suggests that interactions between monoamine systems may be disrupted in these individuals. Using CSF metabolite correlations to study neurotransmitter interactions may have clinical relevance and yields information not available from examining neurotransmitters in isolation.     

可卡因成瘾大鼠脑立体定向核团毁损术前后形态学及单胺类神经递质的变化

目的研究可卡因成瘾大鼠脑形态学的变化及在脑立体定向核团毁损术前后单胺类神经递质的变化。方法采用普通SD大鼠作为实验动物,随机分为对照组、成瘾组、成瘾大鼠毁损伏核组、成瘾大鼠毁损海马组、成瘾大鼠毁损扣带回组、成瘾大鼠毁损伏核-海马-扣带回组。成瘾大鼠每天皮下注射溶解于0.2ml蒸馏水的盐酸可卡因15mg/kg,正常对照组每天皮下注射0.2ml蒸馏水,持续90 d。毁损组分别行不同部位的毁损,3 d后处死,采用高效液相色谱仪(HPLC)脑组织匀浆法检测纹状体的单胺类递质含量,同时观察比较正常、成瘾及毁损后大鼠不同脑区在光镜及电镜下形态学的改变。结果成瘾大鼠纹状体多巴胺含量较正常对照组升高(P<0.01)。毁损前后大鼠单胺类递质无明显变化。在成瘾大鼠的伏核、海马、扣带回观察到核固缩、间质水肿、纤维断裂及坏死。结论长期使用可卡因可以造成大鼠脑组织的损害及纹状体多巴胺含量升高。立体定向核团毁损术前后脑组织单胺类神经递质变化不明显。     

Diffuse brain damage of immediate impact type. Its relationship to 'primary brain-stem damage' in head injury

In a neuropathological analysis of 151 fatal non-missile head injuries, there were 19 cases with focal lesions in the dorsolateral quadrant of the brain-stem in the corpus callosum, and histological evidence of diffuse damage to white matter. Eight of these cases had not experienced a high intracranial pressure during life. All 19 cases had been rendered unconscious at the moment of impact and had remained so or in the persistent vegetative state until death. It is therefore concluded that diffuse damage to white matter may occur as a primary event at the moment of impact, that is, it is one type of immediate impact damage to the brain. It is also concluded that this type of damage is the pathological basis of 'primary brain-stem injury' since in no patient thought clinically to have sustained 'primary brain-stem injury' were abnormalities confined to the brain-stem. Since no patient with this type of brain damage recovered consciousness after injury, it is probable that diffuse damage to white matter is the most important single factor governing the outcome in a patient who sustains a non-missile head injury.     

Psychotropic management of behavioral disorders after head trauma

A rational basis for the psychopharmacologic management of behavioral disturbances after head trauma has been presented that is predicated on research in neurotransmitter changes that evolve subsequent to head trauma. The paucity of human studies in this area mandates the use of experimental models and evidence garnered from provocative challenges to suggest the underlying neurotransmitter profile in various behavioral abnormalities. Multiple neurotransmitter circuits exist that provide parallel, duplicate, and redundant systems for these behaviors. Certainly, alternative explanations could be offered for the examples cited above. Furthermore, measurement of neurotransmitter metabolite concentration in cerebrospinal fluid does not allow specific inferences to be made regarding topographic correlation and neurotransmitter function. Nor does it afford assessment of regional differences in psychotropic influence on neurotransmitter receptors. New imaging techniques (eg, positron emission tomography) will certainly aid in this determination. Current investigations, however, support the concept that neurotransmitter changes do occur after head injury, that these alterations exist during the time that "recovery" occurs, and that psychotropic agents influence this recovery process. Further research is needed to clarify neurotransmitter changes after head injury and to identify psychotropic intervention strategies that facilitate the recovery process.     

Pure motor hemiplegia secondary to brain-stem tumour.

'Pure motor hemiplegia' is a common stroke syndrome defined by Fisher as paralysis of face, arm, and leg on one side, unaccompanied by sensory signs, visual field defect, aphasia, or apractognosia. It occurs almost exclusively in hypertensive patients and carried a good prognosis. We report a case of a normotensive patient in whom pure motor hemiplegia was the presenting feature, not of a cerebrovascular syndrome, but of a pontine glioblastoma. We note that brain-stem tumours may masquerade as brain-stem strokes.     

Clomipramine-induced serum prolactin as a marker for serotonin and dopamine turnover: results of an open label study

Central nervous system (CNS) monoamine deficits have been linked to a number of pathological conditions such as major depressive disorder. Individual biological variations in 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) might account for the variation in responses of neurotransmitter systems observed after the administration of clomipramine. The prolactin response to clomipramine has been widely used to assess CNS functioning. This open label study investigates the prolactin response induced by clomipramine in the plasma of healthy volunteers and whether it is related to changes in monoamine metabolites. The effects of clomipramine challenge on prolactin, 5-HIAA, HVA and MHPG were measured in 12 healthy volunteers. Samples were drawn directly before and 50?min after clomipramine infusion. A statistically significant increase in serum prolactin concentrations was measured in women 50?min after CMI infusion, but not in men. We found no significant increases in the serum monoamine metabolite concentrations 50?min after CMI infusion. Changes in HVA and 5-HIAA correlated statistically significantly and positively with the amount of prolactin release in the whole sample. Furthermore, positive correlations were found between ?(50-0 min) 5-HIAA and ?(50-0 min) HVA, although we did not find a correlation between ?(50-0 min) prolactin and ?(50-0 min) MHPG after clomipramine challenge. The pronounced prolactin release in healthy adult women might indicate a higher physiological sensitivity. Correlations between intra-individual changes in HVA, 5-HIAA and serum prolactin might indicate a central nervous effect of clomipramine on monoamine turnover. We conclude that monoamine changes in relation to prolactin response after clomipramine challenge may be suitable for characterizing the relationship between central serotonergic and dopaminergic function.     

亚低温对重型颅脑创伤患者血清抗脑抗体含量的影响

目的 研究重型颅脑创伤(sTBI)后患者血清抗脑抗体(ABAb)浓度变化及亚低温治疗对血清ABAb浓度的影响,探讨亚低温脑保护机制.方法 选择80例sTBI住院患者,随机分成常温治疗(NT)组和亚低温治疗(HT)组各40例,分别予以常温治疗和亚低温治疗,于伤后第1、3、5、7、14天采血.用酶联免疫吸附(ELISA)法测定血清ABAb浓度,观察各时间点血清ABAb浓度的变化,分析各时间点两组血清ABAb浓度与格拉斯哥预后评分(GOS)的相关性.另取20例健康体检者作为对照组.结果 (1)所有sTBI患者在伤后各时间点血清ABAb浓度高于正常对照组(P＜0.01).(2)HT组于伤后各时间点血清ABAb浓度低于NT组,且差异有统计学意义(P＜0.01).(3)NT组于伤后各时间点血清ABAb浓度与GOS评分呈负相关,出院时HT组预后也较NT组为佳.结论 HT能够降低sTBI患者血清ABAb含量,具有脑保护作用,其脑保护机制可能与HT能减轻血清ABAb介导的损伤性脑细胞炎性反应有关.

Abstract：

Objective To disclose the Probably protective mechanism of mild hypothermia protecting brain through investigating the contents charges of Antibrain-Antibody(ABAb)in serum in patients with severe traumatic brain injury(sTBI) and the influence of mild hypothermia on serum levels of ABAb.Methods A total of 80 cases with sTBI were treated with normothennia - treated (NT) (NT group, re =40)and mild hypothermia( HT) (HT group, n =40) respectively. ELISA was used to measure serum levels of ABAb. Groups at 1、3、5、7 and 14 days after injury to observe the contents changes of ABAb in serum and the influence of mild hypothermia. Simultaneous analysis two groups at each time point of serum ABAb concentration and Glasgow outcome scale (GOS) of relevance was performed Contrast analysis of clinical prognosis for patients in the two groups was carried out to reveal the protective mechanism of mild hypothermia protecting on patients with sTBL 20 serum specimens of normal persons were used as control group. Results (1) All sTBI patients at each time point after injury, serum ABAb levels were higher than the normal control group ( P ＜0.01). (2) Concentration of antibodies in the serum ABAb levels in HT group at each time point was lower than in NT group( P＜0.01). (3) Concentration of serum ABAb levels in NT group at each time point of injury was negatively correlated with the GOS score; prognosis at discharge in HT group was better than in NT group. Conclusions HT can reduce the serum ABAb levels in sTBI patients, improve the prognosis, have brain protective effect The brain protective mechanisms may be related to the mild hypothermia which reduce the serum ABAb - mediated inflammatory damage on brain cells.