蛛网膜下腔出血后铁代谢和神经细胞自噬的关系

正蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后往往伴有早期脑损伤(early brain injury,EBI)。近年来,研究发现自发性SAH后EBI与病人预后有密切的关系,其中铁代谢产生具有神经毒性的氧自由基在EBI中起重要作用~([1])。此外,发生EBI后,作为人体防卫机制的自噬也存在一定程度的激活~([2])。目前,铁代谢及自噬在EBI中的作用机制仍不     

动脉瘤性蛛网膜下腔出血后慢性脑积水

目的探讨动脉瘤性蛛网膜下腔出血后(aSAH)慢性脑积水的发生率及其易患因素。方法回顾性研究2003年1月至2005年9月我科aSAH病例221例,采用单因素及多因素统计方法分析与慢性脑积水发生的相关影响因素。结果慢性脑积水的发生率为12.7%(28/221)。经单因素分析显示,患者年龄、Hunt-Hess级别、Fisher级别、前交通动脉瘤、aSAH次数以及脑室内出血具有统计学意义;多因素logistic回归分析显示,Fisher级别、脑室内出血、aSAH次数、前交通动脉瘤具有统计学意义。结论慢性脑积水为aSAH后一较常见并发症,影响其发生的高危因素包括Fisher级别、脑室内出血、aSAH次数、前交通动脉瘤。对具上述危险因素的aSAH患者应注意跟踪随访,及时诊治。     

动脉瘤性蛛网膜下腔出血后慢性脑积水形成相关危险因素分析

目的探讨动脉瘤性蛛网膜下腔出血(aSAH)后慢性脑积水形成的危险因素。方法回顾分析170例aSAH患者临床资料,应用出血后3周的CT评价aSAH后慢性脑积水;先将可能的危险因素与脑积水之间行显著性检验,再用多元回归加以明确,得到回归方程。结果 aSAH后慢性脑积水易患因素依次为入院时较高Hunt-Hess分级(P=0.006)、反复多次出血(P=0.007)、高龄(P=0.010)。结论 aSAH后慢性脑积水形成为多因素共同作用的结果。     

aSAH患者术后发生延迟性脑缺血的影响因素及风险预警模型构建

目的 探究动脉瘤性蛛网膜下腔出血(aSAH)患者术后发生延迟性脑缺血的影响因素,构建风险预警模型并分析其预测价值。方法 选取2020-01—2023-06河北医科大学附属衡水市人民医院收治的97例aSAH患者为研究对象,均行手术治疗。根据术后是否发生延迟性脑缺血分为发生组(29例)和未发生组(68例)。采用Logistic多因素回归分析aSAH患者术后发生延迟性脑缺血的影响因素,采用受试者工作特征(ROC)曲线评估危险因素对aSAH患者术后发生延迟性脑缺血的预测价值,并构建a SAH患者术后发生延迟性脑缺血的指数方程。结果 单因素分析显示,发生组患者年龄、动脉瘤直径、Hunt-Hess分级、改良Fisher分级、脑积水、脑血管痉挛、中性粒细胞与淋巴细胞计数比值(NLR)等与未发生组比较差异均有统计学意义(P<0.05)。多因素Logistic回归分析显示,Hunt-Hess分级、改良Fisher分级、脑血管痉挛、NLR是影响aSAH患者术后发生延迟性脑缺血的危险因素(P<0.05)。aSAH患者术后发生延迟性脑缺血的指数方程为PI=0.902X₃+0....     

动脉瘤性蛛网膜下腔出血后并发脑血管痉挛的影响因素

目的探讨动脉瘤性蛛网膜下腔出血(aSAH)后并发脑血管痉挛(CVS)的影响因素。方法回顾性分析237例aSAH患者的临床资料,对比并发CVS和无CVS患者的年龄、性别、Hunt-Hess分级、Fisher分级、血压、血脂、白细胞计数等资料,并将有统计学意义的影响因素进行多因素Logistic回归分析,确定独立危险因素和保护因素。结果 237例aSAH患者中65例并发CVS,发生率27.43%;并发CVS和无CVS患者嗜烟、高血脂、高血压、白细胞计数升高、Hunt-Hess分级≥Ⅲ级、Fisher分级≥Ⅲ级、使用小剂量尼莫地平差异有统计学意义(P0.05);Logistic回归分析显示,嗜烟、高血脂、高血压、白细胞计数升高、Hunt-Hess分级≥Ⅲ级、Fisher分级≥Ⅲ级是aSAH患者出血后并发CVS的独立危险因素(P0.05),而使用小剂量尼莫地平是其保护因素(P0.05)。结论临床对于嗜烟、高血脂、高血压、白细胞计数升高、Hunt-Hess分级和Fisher分级较高的aSAH患者应加强早期监测,积极防治CVS的发生。     

脑池及脑池积血在动脉瘤性蛛网膜下腔出血后急性脑积水发生中的作用

目的 探讨脑池及脑池积血在动脉瘤性蛛网膜下腔出血(aSAH)后急性脑积水发生中的作用.方法 对南方医科大学南方医院神经外科201 1年5月至2014年1月经手术治疗且资料完整的306例aSAH患者的临床数据进行回顾性分析,其临床变量进行单因素分析和多因素Logistic回归分析,并对各个脑池的血量进行定量分析.结果 306例患者中有112例发生了急性脑积水,发生率为36.6％.单因素分析表明Fisher分级、脑室积血、动脉瘤的位置、动脉瘤侧别、再出血、治疗方式6项因素比较差异有统计学意义(P＜0.05);多因素Logistic回归分析显示动脉瘤位置与脑室积血为其独立发生因素.在无脑室积血的患者中,急性脑积水的发生率为22.4％,其中脑积水组中的脚间池、右侧侧裂池血量最多,与非脑积水组相比差异有统计学意义(P=0.000;P=0.005).结论 aSAH急性脑积水是多因素共同作用的结果,动脉瘤位置与脑室积血是其独立危险因素;aSAH急性脑积水是梗阻性脑积水,脑池的位置及脑池积血的分布在aSAH急性脑积水发生中有着重要的影响作用;在无脑室积血的aSAH患者中,脚间池、右侧侧裂池的积血血量越大,越容易发生急性脑积水.     

动脉瘤性蛛网膜下腔出血患者贫血与预后的关系

目的 探讨贫血对动脉瘤性蛛网膜下腔出血(aSAH)患者神经功能的影响。方法 以2015年7月1日-2018年9月30日符合条件的aSAH患者为研究对象,前瞻性地记录一般临床资料,在术后第1、3、7 d抽空腹静脉血行血常规检查判断有无贫血; 术后6个月应用扩展格拉斯哥预后评分(GOS-E)评价aSAH患者的神经功能预后情况。结果 136例患者中有57例(41.9%)患者出现贫血,79例(58.1%)患者无贫血。贫血患者预后不良发生率为75.4%(43例),显著高于无贫血患者(57.0%,45例)(χ²=4.949,P=0.026)。多因素logistic回归分析显示动脉瘤位置、WFNS分级、Fisher分级、再出血、脑血管痉挛和贫血是影响神经功能预后的独立因素。结论 aSAH后贫血是导致aSAH患者神经功能不良的危险因素,未来需要进一步探讨aSAH患者输血阈值以及纠正贫血的方案。     

脑脊液引流在早期颅内破裂动脉瘤治疗中的应用

动脉瘤性蛛网膜下腔出血(aneurysmal subarachnoid Hemorrhage,aSAH)造成脑组织损伤的机制非常复杂,其中主要包括颅内压(intracranial pressure,ICP)增高后脑灌注压(cerebral perfusion pressure,CPP)降低、脑血管痉挛(cerebral vasospsm,CVS)、迟发性缺血性神经功能障碍(delayed ischemic neurological deficit,DIND)和脑积水等.针对以上发生机制进行脑脊液引流的辅助治疗对降低aSAH患者的病死率和致残率具有重要意义.     

PVI、CPP与动脉瘤性蛛网膜下腔出血后患者迟发性脑缺血的关系

目的 探讨血小板体积指数(PVI)、脑灌注压(CPP)与动脉瘤性蛛网膜下腔出血(aSAH)后患者迟发性脑缺血(DCI)的关系.方法 选择2016年1月至2018年2月枣庄市立医院诊治的198例aSAH患者,根据是否发生DCI将患者分为DCI组(61例)和NDCI组(137例).检测PVI和CPP,分析其对aSAH后DC...     

神经炎症相关指标与动脉瘤性蛛网膜下腔出血预后的研究进展

动脉瘤性蛛网膜下腔出血(aneurysmal subarachnoid hemorrhage,aSAH)后的迟发性脑缺血是影响病人预后的主要因素.最近的研究发现:神经炎症反应在aSAH后迟发性脑出血的发生、发展及预后过程起重要作用.本文旨在将脑血管功能损伤后,能够指示神经炎症的生物标志物与aSAH预后关系的研究进展作一...     

Midline Shift is Unrelated to Subjective Pupillary Reactivity Assessment on Admission in Moderate and Severe Traumatic Brain Injury

Background

Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) is defined as brain injury occurring within 72 h of aneurysmal rupture. Although EBI is the most significant predictor of outcomes after aSAH, its underlying pathophysiology is not well understood. We hypothesize that EBI after aSAH is associated with an increase in peripheral inflammation measured by cytokine expression levels and changes in associations between cytokines.

Methods

aSAH patients were enrolled into a prospective observational study and were assessed for markers of EBI: global cerebral edema (GCE), subarachnoid hemorrhage early brain edema score (SEBES), and Hunt–Hess grade. Serum samples collected at ≤ 48 h of admission were analyzed using multiplex bead-based assays to determine levels of 13 pro- and anti-inflammatory cytokines. Pairwise correlation coefficients between cytokines were represented as networks. Cytokine levels and differences in correlation networks were compared between EBI groups.

Results

Of the 71 patients enrolled in the study, 17 (24%) subjects had GCE, 31 (44%) subjects had SEBES ≥ 3, and 21 (29%) had HH ≥ 4. IL-6 was elevated in groups with GCE, SEBES ≥ 3, and HH ≥ 4. MIP1β was independently associated with high-grade SEBES. Correlation network analysis suggests higher systematic inflammation in subjects with SEBES ≥ 3.

Conclusions

EBI after SAH is associated with increased levels of specific cytokines. Peripheral levels of IL-10, IL-6, and MIP1β may be important markers of EBI. Investigating systematic correlations in addition to expression levels of individual cytokines may offer deeper insight into the underlying mechanisms related to EBI.

     

丁苯酞注射液对动脉瘤性蛛网膜下腔出血早期脑损伤的作用与机制探讨

目的 探讨丁苯酞注射液对动脉瘤性蛛网膜下腔出血（aneurysmal subarachnoid hemorrhages,aSAH） 患者早期脑损伤的作用与机制。     

INT-777 attenuates NLRP3-ASC inflammasome-mediated neuroinflammation via TGR5/cAMP/PKA signaling pathway after subarachnoid hemorrhage in rats

BackgroundInflammasome-mediated neuroinflammation plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of the TGR5 receptor has been shown to be neuroprotective in a variety of neurological diseases. This study aimed to investigate the effects of the specific synthetic TGR5 agonist, INT-777, in attenuating NLRP3-ASC inflammasome activation and reducing neuroinflammation after SAH.MethodsOne hundred and eighty-four male Sprague Dawley rats were used. SAH was induced by the endovascular perforation. INT-777 was administered intranasally at 1 h after SAH induction. To elucidate the signaling pathway involved in the effect of INT-777 on inflammasome activation during EBI, TGR5 knockout CRISPR and PKA inhibitor H89 were administered intracerebroventricularly and intraperitoneally at 48 h and 1 h before SAH. The SAH grade, short- and long-term neurobehavioral assessments, brain water content, western blot, immunofluorescence staining, and Nissl staining were performed.ResultsThe expressions of endogenous TGR5, p-PKA, and NLRP3-ASC inflammasome were increased after SAH. INT-777 administration significantly decreased NLRP3-ASC inflammasome activation in microglia, reduced brain edema and neuroinflammation, leading to improved short-term neurobehavioral functions at 24 h after SAH. The administration of TGR5 CRISPR or PKA inhibitor (H89) abolished the anti-inflammation effects of INT-777, on NLRP3-ASC inflammasome, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-a), and neutrophil infiltration at 24 h after SAH. Moreover, early administration of INT-777 attenuated neuronal degeneration in hippocampus on 28 d after SAH.ConclusionsINT-777 attenuated NLRP3-ASC inflammasome-dependent neuroinflammation in the EBI after SAH, partially via TGR5/cAMP/PKA signaling pathway. Early administration of INT-777 may serve as a potential therapeutic strategy for EBI management in the setting of SAH.     

蛛网膜下腔出血后神经炎症反应的研究进展

动脉瘤性蛛网膜下腔出血（aneurysmal subarachnoid hemorrhage,aSAH）是一种常见的脑血 管疾病。临床手术技术的提高虽然能够治疗动脉瘤,降低因再次出血而导致患者死亡的概率。但是, 目前尚无有效的针对蛛网膜下腔出血并发症的治疗方法。神经系统的炎症反应在蛛网膜下腔出血 后的病理过程中起着重要的作用,现研究已表明炎症反应与脑血管痉挛以及脑组织损伤相关。因此, 大量的临床前研究也针对神经炎症与aSAH之间的相关性展开,并发现炎症介质在其中发挥着重要的 作用。本文就已知的aSAH后神经炎症反应及其发生机制作一综述。     

事件相关电位诊断动脉瘤性蛛网膜下腔出血后认知功能障碍的研究

目的 评价事件相关电位N200和P300评估动脉瘤性蛛网膜下腔出血（aneurysmal subarachnoid hemorrhage,aSAH）患者早期认知障碍的价值。 方法 连续纳入2013年10月-2014年12月于首都医科大学附属北京天坛医院住院治疗的aSAH患者, 按照入院14±3 d是否存在认知障碍分为aSAH认知障碍组和aSAH无认知障碍组,同时纳入年龄、性 别相匹配的正常人群作为对照组。所有入组患者完成MMSE、MoCA量表评定及脑电图事件相关电位 N200和P300潜伏期的测定[额中线（frontal midline,Fz）、中央中线（central midline,Cz）、顶中线（parietal midline,Pz）三个部位]。比较对照组、aSAH认知障碍组和aSAH无认知障碍组间N200及P300潜伏期的 差异。分析N200和P300诊断aSAH患者认知障碍的敏感性和特异性。另外,通过单因素和多因素分析, 明确aSAH患者发生早期认知障碍的独立危险因素。 结果 共入组62例aSAH患者,存在认知功能障碍者45例（72.6%）,无认知障碍者17例（27.4%）;对 照组30例患者。aSAH无认知障碍组和aSAH认知障碍组Cz、Pz和Fz的P300潜伏期均长于正常对照组, Cz和Pz的N200潜伏期长于正常对照组,aSAH认知障碍组Fz的N200潜伏期长于正常对照组,差异有统 计学意义;与aSAH无认知障碍组相比,aSAH认知障碍组Cz、Pz和Fz的P300及N200潜伏期均延长,差 异有统计学意义。事件相关电位N200潜伏期分界值为257.0～261.0 ms时,诊断认知障碍的敏感度为 67.1%～79.4%,特异度为74.2%～81.5%;事件相关电位P300潜伏期分界值为347.0～349.5 ms时,诊 断认知障碍的敏感度为88.1%～94.0%,特异度为78.9%～82.1%。多因素分析结果显示,低受教育年 限（OR 1.19,95%CI 1.02～2.15,P =0.037）及Hunt-Hess分级3级（OR 1.65,95%CI 1.05～1.92,P =0.013） 是aSAH患者出现早期认知障碍的独立危险因素。 结论 事件相关电位N200和P300可以作为判断aSAH患者早期认知功能障碍的一种有用的、客观的 检查工具。     

基于病历会商制度的动脉瘤性蛛网膜下腔出血医疗效率改进模式——一种持续高效的脑血管病医师继续教育方式

目的 探讨基于病历会商制度的动脉瘤性蛛网膜下腔出血（aneurysmal s ubarachnoid h emorrhages， aSAH）医疗服务效率改进模式对脑血管病医师的继续教育作用及其成效分析。 方法 首都医科大学附属北京天坛医院自2013年7月开始对脑血管病医师进行基于病历会商制度的 aSAH治疗效率持续改进模式教育，评价2013年1月-6月与2017年7月-12月两个时间段脑血管病医师对 aSAH患者发病72 h内介入栓塞或外科夹闭术治疗率变化及患者到院距接受治疗平均时间的差异。 结果 通过基于病历会商制度的aSAH医疗服务效率改进模式的继续教育制度，脑血管病医师对 aSAH患者的治疗效率有显著改善[患者发病72h治疗率：83.6% vs 55.3%，P＜0.001；患者到院距接受 治疗的平均时间：（45.0±31.3）h vs（78.6±51.8）h，P＜0.001]。 结论 基于病历会商制度的aSAH医疗服务效率改进模式是一种持续高效的脑血管病医师继续教育 方式。     

Lactate and Lactate Dehydrogenase in Cistern as Biomarkers of Early Brain Injury and Delayed Cerebral Ischemia of Subarachnoid Hemorrhage

Objective: The pathophysiology of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) has not been fully evaluated. The aim of this study was to evaluate the dynamics of lactate and lactate dehydrogenase (LDH) in carotid cisternal cerebrospinal fluid (CSF), and to discuss their effectiveness as markers of early brain injury (EBI) and DCI following aSAH. Patients and Methods: Among 91 consecutive aSAH patients treated between January 2012 and March 2019 at National Hospital Organization Beppu Medical Center, 19 patients (20.9%) were eligible for this retrospective study. Concentrations of lactate and LDH in carotid cisternal CSF within 14 days after onset of aSAH were evaluated. Results: Six of the 19 patients (31.6%) had a history of DCI. Both lactate and LDH levels in carotid cisternal CSF were significantly higher in the DCI group than in the non-DCI group on postbleeding day (PBD) 1-2, 3-4, and 5-6. Interestingly, neither lactate nor LDH levels in blood differed significantly between DCI and non-DCI groups on PBD 1-2. Conclusions: Lactate and LDH concentrations in carotid cisternal CSF may vividly reflect the EBI and may thus represent predictive biomarkers of DCI following aSAH.     

急性期胰岛素样生长因子-1对动脉瘤性蛛网膜下腔出血院内并发症及短期预后的预测作用

目的 探讨胰岛素样生长因子-1（insulin like growth factor-1,IGF-1）水平对动脉瘤性蛛网膜下腔出 血（aneurysmal subarachnoid hemorrhage,aSAH）患者院内并发症及出院时临床预后的预测价值。 方法 连续入组发病72 h内的aSAH患者及健康对照。在动脉瘤闭塞术前采集血样,测定血浆IGF-1水 平。对患者基本信息,神经内分泌因子、院内并发症及结局进行分析,用Logistic回归确定院内并发症 及出院时预后不良（mRS评分＞2分）的预测因素,计算预测因素的受试者工作特征曲线下面积。 结果 共入组118例aSAH患者和122例健康对照者。aSAH患者血浆IGF-1水平较健康对照低[69.00 （50.98,93.85）ng/mL vs 81.05（69.40,102.78）ng/mL,P <0.0001]。37例（31.4%）患者出院时预 后不良。IGF-1浓度越低（OR 0.971,95%CI 0.946～0.996,P =0.0262）、入院时Hunt-Hess分级3～5 级（OR 4.995,95%CI 1.331～18.747,P =0.0007）、住院期间发生迟发型脑缺血（OR 46.100,95%CI 11.152～190.566,P <0.0001）及脑积水（OR 7.768,95%CI 1.088～55.463,P =0.0284）的患者预后不良 风险增高。IGF-1与Hunt-Hess分级、迟发型脑缺血的预测价值基本相同（P >0.05）。71例（60.2%）患者 住院期间发生至少1种并发症。仅有入院时I GF-1浓度（OR 0.984,95%CI 0.973～0.996,P =0.0082）对 院内并发症有预测价值。 结论 aSAH急性期患者血浆IGF-1浓度越低,住院期间并发症发生率越高,出院时功能预后越差。     

颅内动脉瘤性蛛网膜下腔出血患者血压变异性与预后的相关性研究

目的 本文旨在探讨动脉瘤性蛛网膜下腔出血（aneurysmal subarachnoid hemorrhage，aSAH）患者血压 变异性对预后的影响。      

Association of cerebrospinal fluid advanced oxidation protein products levels with early brain injury and prognosis of aneurysmal subarachnoid hemorrhage: A preliminary prospective study

ObjectivesIn this study, we investigated the time course in the cerebrospinal fluid (CSF) advanced oxidation protein products (AOPPs) levels in patients with aneurysmal subarachnoid hemorrhage (aSAH), and ascertained the relationship between the levels of AOPPs and early brain injury (EBI), hydrocephalus and prognosis of patients with aSAH.MethodsWe measured the CSF AOPPs levels in 50 patients with aSAH at 1–3 d, 4–6 d, 7–9 d, and 10–12 d after hemorrhage. The modified Fisher grades, Hunt-Hess grades, CSF IL-6 levels, peripheral blood count of white blood cells, cerebral edema scores and hydrocephalus were used to assess the severity of brain injury. Modified Rankin Scale (mRS) scores were used to assess the prognosis. Patients with mRS scores greater than 2 were considered to have a poor outcome.ResultsCSF AOPPs levels were significantly higher in patients with aSAH with poor prognosis, compared to patients with good prognosis and peaked in the early stage. Among patients with aSAH, the levels of CSF AOPPs on days 1–3 were significantly correlated with modified Fisher grades, Hunt-Hess grades, CSF IL-6 levels, peripheral blood count of white blood cells, and cerebral edema scores. Also, in patients with hydrocephalus, early CSF AOPPs levels were significantly elevated. Levels of CSF AOPPs in aSAH patients on days 1–3, 4–6, and 7–9 were independently associated with poor prognosis at the 90-day follow-up, and the optimal area under the curve (AUC) values for CSF AOPPs levels were found on days 1–3.ConclusionsAOPPs may serve as the potential biomarker to assess the severity of EBI and prognosis in patients with aSAH.