中性粒细胞-淋巴细胞比值在颅脑损伤预后评估中的作用

目的 探讨中性粒细胞-淋巴细胞比值（NLR）在颅脑损伤（TBI）预后评估中的作用。方法 回顾性分析2015年3月~2019年1月收治的105例TBI的临床资料。伤后6个月,采用GOS评分评估预后,1~3分为预后不良,4~5分为预后良好。采用多因素logistic回归分析检验预后不良危险因素,采用受试者工作特征（ROC）曲线分析NLR对TBI病人6个月预后的预判价值。结果 105例中,预后不良34例,发生率为32.38%。多因素logistic回归分析结果显示,入院时GCS评分≤8分、颅内压增高、瞳孔对光反射消失和NLR均是TBI病人伤后6个月预后不良的独立危险因素（P<0.05）。ROC曲线分析结果显示NLR的最佳临界值为4.12,此时灵敏度为85.7%,特异度为81.6%,当NLR≥4.12时,TBI病人预后不良的发生率高达93.6%。结论 入院时NLR水平可作为预测TBI伤后6个月预后不良的参考指标,可早期、迅速、准确判断病人预后,及时有效地采取干预措施,改善病人预后     

颅脑损伤后外周血白细胞和中性粒细胞的变化及其与继发性脑损伤的关系

一、资料与方法1.一般资料:选取非手术治疗的颅脑损伤患者共63例,男41例,女22例,年龄9—72岁,平均41.8岁,患者均合并有不同大小的脑内血肿。2.方法:于入院当时、24h、48h、72h及168h五个时间段检测以下指标:(1)抽取患者静脉血2ml,进行白细胞计数及     

放射性脑损伤大鼠血中性粒细胞CD18的表达

目的 探讨中性粒细胞CD18的表达变化与放射性脑损伤的关系。方法 用10MeV X射线垂直照射大鼠全脑，接受剂量30Gy。照射2周后，颈总动脉取血．梯度离心、取中性粒细胞层．用Northern杂交分析流式细胞术分析法，测定血液中性粒细胞CD18 mRNA表达水平和膜蛋白数量。结果 大鼠脑组织接受照射后．光镜下出现明显的细胞损伤改变，血液中性粒细胞CD18 mRNA表达水平和膜蛋白数量在照射后均有明显提高。结论 CD18介导的中性粒细胞粘附参与了放射性脑损伤的发生和发展。     

中性粒细胞明胶酶相关载脂蛋白在大鼠脑出血后继发性脑损伤中的作用研究

目的探讨中性粒细胞明胶酶相关载脂蛋白(NGAL)在脑出血(ICH)后继发性脑损伤中的作用。方法采用Ⅶ胶原酶制作ICH模型,将90只雄性SD大鼠随机分为3组:正常对照组(10只)、假手术组(40只)和ICH模型组(40只)。分别在ICH后6 h、24 h、72 h和7 d四个时间点对大鼠进行神经功能缺损评分;用免疫组化及RT-q PCR来观察不同时间点脑组织NGAL及MMP-9表达情况。结果免疫组化及RT-q PCR结果显示ICH后模型组各时间点均可见大量NGAL、MMP-9阳性细胞及NGAL mRNA表达,且明显高于正常组及假手术组(P0.05)。ICH模型组NGAL与MMP-9蛋白表达呈正相关(P0.01)。ICH模型组NGAL、MMP-9蛋白表达均与大鼠神经功能缺损评分呈正相关(P0.05)。结论 ICH后NGAL表达明显增加,提示NGAL可能参与了脑出血后继发性脑损伤,并可能通过调节MMP-9的活性从而发挥作用,但NGAL是否为MMP-9的上游调控因子尚有待进一步研究。     

中性粒细胞在胶质瘤中的作用机制及靶向治疗的研究进展

中性粒细胞作为肿瘤微环境的重要成员,广泛分布于循环系统中,而脑实质内的中性粒细胞可能更多地来源于颅骨和邻近的脊椎骨髓。最近的研究表明,中性粒细胞在与胶质瘤细胞接触后发生表型改变,并表现出多种功能,包括参与胶质瘤的恶性进展、免疫抑制和抗肿瘤作用。在早期阶段,中性粒细胞通过抗体依赖性细胞毒性机制对肿瘤细胞具有抑制作用。随着接触时间的延长,中性粒细胞抗肿瘤作用逐渐减弱,而促肿瘤作用逐渐增强。此外,中性粒细胞还通过各种因子和受体与其他免疫细胞相互作用,进一步促进胶质瘤增殖、侵袭、血管生成和免疫抑制。因此,针对中性粒细胞的靶向治疗可能成为新一代免疫疗法,并提高癌症治疗的疗效,这些策略主要涉及抑制中性粒细胞的招募、促进中性粒细胞的重编程和耗竭。该综述总结了中性粒细胞的起源、功能状态、免疫作用等研究,以及它对胶质瘤的影响及靶向治疗的前景。国际神经病学神经外科学杂志, 2024, 51(2): 76-84]     

弹性蛋白酶诱导脑动脉瘤模型的制作方法及意义

脑动脉瘤模型的建立有多种方法,弹性蛋白酶诱导建立脑动脉瘤模型的制作方法日益被广泛应用,该方法操作方便、周期短,组织病理结构也接近于临床人动脉瘤。本文回顾弹性蛋白酶诱导脑动脉瘤的制作方法,并阐明其在建立脑动脉瘤模型方面的意义,为进一步研究动脉瘤的发生发展和转归预后提供良好的实验平台。     

异丙酚预处理对大鼠脑缺血再灌注损伤早期中性粒细胞弹性蛋白酶活性及炎性因子表达的影响

目的 探讨异丙酚预处理对大鼠脑缺血再灌注(IR)损伤早期中性粒细胞弹性蛋白酶(NE)活性及炎性因子肿瘤坏死因子(TNF)-α和白介素(IL)-1β表达的影响.方法 健康雄性SD大鼠50只,随机分为正常对照组(NC组)、IR组、异丙酚低剂量组(P1组,50 mg/kg)、中剂量组(P2组,100 mg/kg)和高剂量组(P3组,150 mg/kg).采用线栓法建立大鼠大脑中动脉局灶性IR损伤模型.各异丙酚组分别于脑缺血前10min经腹腔注射相应剂量的异丙酚.大鼠脑缺血2h、再灌注24h给予神经功能缺损评分,采用酶联免疫吸附法检测脑组织NE活性及TNF-α和IL-1β的表达.结果 各异丙酚组神经功能缺损评分明显低于IR组(均P＜0.01);与NC组比较,IR组和各异丙酚组脑组织NE活性及TNF-α、IL-1β表达明显升高(均P＜0.01);与IR组比较,各异丙酚组NE活性及TNF-α、IL-1β表达明显降低(均P＜0.01);P2组NE活性及TNF-α、IL-1β表达明显低于P1组和P3组(均P＜0.01).结论 异丙酚预处理可抑制脑组织NE活化和TNF-α、IL-1β过度表达,降低炎性反应,对脑组织IR损伤早期具有保护作用;异丙酚100 mg/kg预处理的作用最佳.     

急性脑梗死患者中性粒细胞粘附分子表达的变化及意义探讨

目的探讨急性脑梗死(cerebral infarction,CI)患者中性粒细胞(polymorphonuclear neutrophil,PMN)表面粘附分子CD62L和CD11b/CD18表达及其意义。方法选择急性血栓形成性脑梗死患者40例,年龄、性别等与之匹配的健康志愿者30例作为对照。运用流式细胞仪对所有对象检测外周血中PMN表面粘附分子CD62L和CD11b/CD18表达。结果相对于正常组粘附分子CD62L平均抗体阳性表达率(73.316±1.276)%,CI组(61.058±8.925)%显著降低(P<0.001);相对于正常组CD11b/CD18平均阳性表达率(20.031±0.540)%,CI组(55,598±0.540)%显著升高。CI组内部CD62L、CD11b/CD18相关分析,二者呈明显负相关,相关系数为r=-0.259(P<0.001)。结论在急性血栓形成性脑梗死的急性期,PMN处于活化状态,表现为粘附分子CD62L表达的下调和CD11b/CD18表达的上调。以细胞粘附为表现的PMN活化加快了血栓的进程,可能是血栓形成的重要发病原因之一。     

中性粒细胞淋巴细胞比值对术后并发颅内感染患者的预测价值

目的探讨术后中性粒细胞淋巴细胞比值（NLR）动态变化对颅脑外伤术后患者颅内感染的预测价值。 方法选取扬州大学附属医院重症医学科自2012年1月至2018年12月收治的116例颅脑外伤并发术后颅内感染患者。根据患者术后第3天NLR的检测结果,NLR≥3为高NLR组,NLR<3为低NLR组,比较2组患者的临床预后情况。 结果高NLR组患者在术后第3天NLR值明显升高,与低NLR组比较差异具有统计学意义（2.24±0.68 vs 4.72±1.21,P<0.05）。高NLR组患者颅内感染发生10例（19%）,低NLR组颅内感染发生4例（6%）,2组比较差异具有统计学意义（P=0.033）。NLR：曲线下面积（AUC）=0.894,95%CI：0.795~0.993;PCT：AUC=0.895,95%CI：0.764~1.027;CRP：AUC=0.898,95%CI：0.814~0.981。高NLR组患者ICU入住时间和机械通气时间均长于低NLR组,差异具有统计学意义（18.4±8.7 vs 13.2±5.4,P=0.000;10.3±4.7 vs 5.3±4.1,P=0.000）。高NLR组患者病死率高于低NLR组,差异具有统计学意义（P=0.026）。 结论术后升高的NLR对颅脑外伤术后患者颅内感染的发生具有较好的临床预测价值,升高的NLR值和不良预后密切相关。     

白介素6在脂多糖致大鼠脑水肿中的表达

目的 探讨白介素6（IL-6）在脂多糖（LPS）致大鼠脑水肿发病过程中的表达及纳洛酮对其干预作用。方法 SD大鼠84只，对照组（NS组）28只，0．2ml生理盐水颈内动脉注射；内毒素组（LPS组）28只，颈内动脉注射LPS 200μg；纳洛酮治疗组（NAL组）28只，颈内动脉注射LPS后10min、1h、2h、6h、12h及处死前2h腹腔注射纳洛酮lmg／kg。于不同时间点测定脑组织匀浆IL-6的含量。干湿法测定脑组织含水量，甲酰胺法测定伊文思兰（EB）含量。结果 LPS组脑组织含水量和EB含量显著高于NS组（P〈0．01）。NAL组脑组织含水量和EB含量显著低于LPS组（P〈0．01），但仍较NS组高（P〈0．01）。注射LPS后4h，LPS组脑组织IL-6含量即增加，于6h达高峰，与NS组比较，差异有统计学意义（P〈0．01）。NAL组IL-6含量低于LPS组（P〈0．05或P≤O．01），但高于NS组（P〈0．01）。LPS组脑组织含水量和EB含量呈正相关（r=0．743，P〈0．01），IL-6含量与含水量呈正相关（r=0．459，P〈0．05），IL-6含量与EB含量呈正相关（r=0．568，P〈0．05）。结论IL-6参与脑水肿的发生发展，纳洛酮可以抑制IL-6的生成，减轻脑水肿。     

Role of neutrophil elastase in compression-induced spinal cord injury in rats

We have previously demonstrated the importance of activated neutrophils in compression-induced spinal cord injury (SCI) in rats. In the present study, we investigate the action of neutrophil elastase in posttraumatic SCI, using two neutrophil elastase inhibitors (Eglin C and L658,758). SCI was induced by applying a 20-g weight to the spinal cord for 20 min at the level of T12, resulting in hindlimbs motor disturbances, which, when evaluated using a inclined-plane test, were significantly attenuated by Eglin C or L658,758. Histologic examination revealed that intramedullary hemorrhages observed 24 h after trauma were markedly attenuated in these agents. These inhibitors also significantly decreased neutrophil accumulation as shown by myeloperoxidase activity in the damaged spinal cord segment. Induction of leukocytopenia had the same effects as Eglin C or L658,758. These findings implicated neutrophil elastase in SCI. The enzyme may induce vascular damage leading to spinal cord ischemia.     

白介素6在脂多糖致大鼠脑水肿中的表达

目的 探讨白介素6(IL-6)在脂多糖(LPS)致大鼠脑水肿发病过程中的表达及纳洛酮对其干预作用.方法 SD大鼠84只,对照组(NS组)28只,0.2ml生理盐水颈内动脉注射;内毒素组(LPS组)28只,颈内动脉注射LPS 200μg;纳洛酮治疗组(NAL组)28只,颈内动脉注射LPS后10min、1h、2h、6h、12h及处死前2h腹腔注射纳洛酮1mg/kg.于不同时间点测定脑组织匀浆IL-6的含量.干湿法测定脑组织含水量,甲酰胺法测定伊文思兰(EB)含量.结果 LPS组脑组织含水量和EB含量显著高于NS组(P＜0.01).NAL组脑组织含水量和EB含量显著低于LPS组(P＜0.01),但仍较NS组高(P＜0.01).注射LPS后4h,LPS组脑组织IL-6含量即增加,于6h达高峰,与NS组比较,差异有统计学意义(P＜0.01).NAL组IL-6含量低于LPS组(P＜0.05或P≤0.01),但高于NS组(P＜0.01).LPS组脑组织含水量和EB含量呈正相关(r=0.743,P＜0.01),IL-6含量与含水量呈正相关(r=0.459,P＜0.05),IL-6含量与EB含量呈正相关(r=0.568,P＜0.05).结论 IL-6参与脑水肿的发生发展,纳洛酮可以抑制IL-6的生成,减轻脑水肿.     

Viral mimetic triggers cerebral arteriopathy in juvenile brain via neutrophil elastase and NETosis

Stroke is among the top ten causes of death in children but has received disproportionally little attention. Cerebral arteriopathies account for up to 80% of childhood arterial ischemic stroke (CAIS) cases and are strongly predictive of CAIS recurrence and poorer outcomes. The underlying mechanisms of sensitization of neurovasculature by viral infection are undefined. In the first age-appropriate model for childhood arteriopathy—by administration of viral mimetic TLR3-agonist Polyinosinic:polycytidylic acid (Poly-IC) in juvenile mice—we identified a key role of the TLR3-neutrophil axis in disrupting the structural-functional integrity of the blood-brain barrier (BBB) and distorting the developing neurovascular architecture and vascular networks. First, using an array of in-vivo/post-vivo vascular imaging, genetic, enzymatic and pharmacological approaches, we report marked Poly-IC-mediated extravascular leakage of albumin (66kDa) and of a small molecule DiI (∼934Da) and disrupted tight junctions. Poly-IC also enhanced the neuroinflammatory milieu, promoted neutrophil recruitment, profoundly upregulated neutrophil elastase (NE), and induced neutrophil extracellular trap formation (NETosis). Finally, we show that functional BBB disturbances, NETosis and neuroinflammation are markedly attenuated by pharmacological inhibition of NE (Sivelestat). Altogether, these data reveal NE/NETosis as a novel therapeutic target for viral-induced cerebral arteriopathies in children.     

大黄对重型颅脑损伤后应激性溃疡的预防作用

目的 探讨重型颅脑损伤后应激性溃疡的发生机制及大黄对重型颅脑损伤后应激性溃疡的预防作用.方法 成年雄性SD大鼠40只按随机数字表法分为假手术组、模型组、大黄治疗组和奥美拉唑治疗组,每组10只.后3组大鼠采用改良的Feeney自由落体法制备重型颅脑损伤模型,大黄治疗组和奥美拉唑治疗组大鼠在模型后分别给予大黄粉悬浊液灌胃和奥美拉唑口服.模型后2、6、24 h对各组大鼠行神经损害严重程度评分(NSS);于模型后24 h采用激光血流仪探头检测各组大鼠胃黏膜血流(pu),取胃前壁组织观察并测量黏液层厚度(μm);HE染色观察胃黏膜的病理变化并计算溃疡指数(UI).结果 与假手术组比较,模型组、大黄治疗组和奥美拉唑治疗组大鼠NSS评分较低,差异有统计学意义(P＜0.05);与模型组比较,大黄治疗组和奥美拉唑治疗组大鼠模型后24 h胃黏膜血流和黏液层厚度增加,溃疡指数降低,且大黄治疗组大鼠胃黏膜血流和黏液层厚度均高于奥美拉唑治疗组,差异有统计学意义(P＜0.05);大鼠NSS评分、胃黏膜血流、黏液层厚度与溃疡指数之间均呈现明显的负相关关系(r=-0.429,P=0.002;r=-0.542,P=0.013;r=-0.465,P=0.024).而胃黏膜血流和胃黏膜黏液层厚度之间呈正相关关系(r=0.680,P=0.001).结论 大黄对颅脑损伤后应激性溃疡有预防性作用,且不减少黏液的分泌,但对颅脑损伤大鼠短期内的行为学评分无明显改善.

Abstract：

Objective To explore the mechanism of stress ulcer induced by severe brain injury and prophylactic effect of rhubarb on this stress ulcer in rats. Methods Forty adult male SD rats were equally randomized into sham-operated group, model group, rhubarb treatment group and omeprazole treatment group (n=10). Rat models of craniocerebral injury in the later 3 groups were established according to modifiod Feeney's method; and then, rhubarb in a suspension manner was given by way of ig into the rhubarb treatment group and omeprazole was given orally to rats in the omeprazole treatment group. The neurological severity scale (NSS) was performed 2, 6 and 24 h after the brain injury. The gastric mucosal blood flow (GMBF) was measured by probe test with laser Joppler flowmetry; thickness of the slime layer was measured; pathological changes of mucous mermbrane were observed by HE staining and the ulcer index was calculated 24 h after the brain injury. Results As compared with the sham-operated group, the other 3 groups enjoyed significantly lower scores of NSS (P＜0.05). Thickness of the slime layer and GMBF in the rhubarb and omeprazole treatment groups were obviously increased,and ulcer index in them was obviously decreased as compared with those in the model group (P＜0.05);the levels of thickness of the slime layer and GMBF in the rhubarb treatment group were significantly higher than those in the omeprazole treatment group (P＜0.05). The scores of NSS, thickness of the slime layer and GMBF were negatively correlated to the ulcer index(r=-0.429, P=0.002; r=-0.542, P=0.013;r=-0.465, P=0.024). Positive correlation was noted between thickness of the slime layer and GMBF(r=0.680, P=0.001). Conclusion Prophylactic effect ofrhubarb on severe brain injury induced stress ulcer is noted in rats. But the rhubarb may neither reduce the mucus secretion nor improve the scores of behavioral evaluation in a short term.     

Surgically induced brain injury in rats: the effect of erythropoietin

Brain tissue at the edge of a surgical resection site is at risk for damage from direct trauma, retractor stretch, hemorrhage, edema, and electrocautery. In this study we used a new rodent model of surgically induced brain injury (SBI) to study this tissue at the edge of a resection site. The SBI model entails stereotaxic resection of part of the right frontal lobe. We tested pretreatment with erythropoietin, a known neuroprotectant, for protective effects in this model. Three groups of male Sprague-Dawley rats (280-330g) were used: SBI without treatment (n=63), SBI with EPO treatment (n=76), and Sham surgery (n=12). Rats were sacrificed 24h, 72h, and 7 days after SBI or Sham surgery. Postoperative assessment included mortality, histology, immunohistochemistry, Evans blue exudation, brain water content, and magnetic resonance imaging. No difference was found between untreated and EPO-treated groups in mortality, histology, TUNEL, magnetic resonance imaging, or blood-brain-barrier breakdown. The EPO-treated group had statistically more brain water content at 24h than the untreated group. Immunohistochemistry demonstrated a qualitative increase in VEGF in the EPO-treatment group. We conclude that EPO does not ameliorate damage in SBI, and may increase brain edema early after surgery.     

液压冲击脑损伤大鼠脑皮层IκBα的表达研究

目的 研究大鼠液压冲击脑损伤时KB抑制蛋白仅（inhibitorysubunitofNF．KB，IKBa）表达变化规律。方法 将60只SD大鼠随机分为两组：损伤组：48只大鼠行液压冲击打击，制作大脑损伤模型。对照组：12只大鼠仅行颅骨钻孔术。使用免疫组化及western blot分别测定大脑皮层细胞浆内IKBa的表达变化情况。免疫组化以细胞浆出现棕黄色颗粒为阳性结果，westernblot以醋酸纤维素膜上出现棕色条带为阳性结果。结果 损伤后1h，IKBa表达开始下降，12h降到最低点，损伤后24h表达开始回升，5d逐步恢复正常。结论 IKBa活性变化可作为急性创伤性颅脑损伤时炎症反应程度的一项观测指标，通过抑制IKBa磷酸化降解环节，可发现一条抑制炎症反应的新途径。     

一种大鼠激光脑损伤模型的建立

目的建立一种稳定、可靠的大鼠激光脑损伤动物模型。方法成年SD大鼠100只,体质量（220±30）g,随机分为假手术对照组（n=25）和激光脑损伤组（n=75）;激光脑损伤组分别用14J、28J和56J能量激光照射致伤动物,根据伤后处理时间点每组再分为5个亚组,即伤后6h、24h、48h、72h和7d组,每亚组5只;假手术组不予激光照射。检测照射后不同时间点脑水肿指数、神经功能评分、血压和光、电镜病理形态变化。结果不同能量组伤后脑水肿指数、神经功能评分、血压和光、电镜病理形态变化不同;假手术对照组无明显改变。结论工作距离0．5cm,工作电流0．2mA,波长10．64μm,28J能量激光可以造成稳定的激光脑损伤动物模型。     

肺炎链球菌溶血素致脑损伤中细胞凋亡及凋亡诱导因子的变化及意义

目的 探讨肺炎链球菌溶血素(PLY)致感染性脑损伤中细胞凋亡及凋亡诱导因子(AIF)的表达及意义. 方法 SD大鼠80只按随机数字表法分为PLY组[颈内动脉注射0.2 mL(7μg) PLY]和生理盐水(NS)组(颈内动脉注射等体积NS),每组40只.每组按观察时间点分为6h、12h、24 h、48 h4个亚组,每亚组10只,其中5只注射髓,甲酰胺法测定脑组织EB含量判断血脑屏障(BBB)的破坏程度.5只不注射EB,取脑组织切片,应用免疫组化和TUNEL染色分别检测脑组织神经元特异性烯醇化酶(NSE)、胶质纤维酸性蛋白(GFAP)、AIF蛋白含量和细胞凋亡. 结果 与NS组比较,造模后各时间点PLY组大鼠脑组织EB、NSE、GFAP、AIF蛋白含量均较高,细胞凋亡较多,差异均有统计学意义(P＜0.05); PLY组大鼠脑组织凋亡细胞数与AIF蛋白的表达呈正相关关系(r=0.959,P=0.000). 结论 细胞凋亡参与了PLY诱导的脑损伤的发展过程,AIF可能介导了神经细胞的凋亡.