Interleukin 6 and Aneurysmal Subarachnoid Hemorrhage. A Narrative Review

Interleukin 6 (IL-6) is a prominent proinflammatory cytokine. Neuroinflammation in general, and IL-6 signaling in particular, appear to play a major role in the pathobiology and pathophysiology of aneurysm formation and aneurysmal subarachnoid hemorrhage (SAH). Most importantly, elevated IL-6 CSF (rather than serum) levels appear to correlate with delayed cerebral ischemia (DCI, “vasospasm”) and secondary (“vasospastic”) infarctions. IL-6 CSF levels may also reflect other forms of injury to the brain following SAH, i.e., early brain damage and septic complications of SAH and aneurysm treatment. This would explain why many researchers have found an association between IL-6 levels and patient outcomes. These findings clearly suggest CSF IL-6 as a candidate biomarker in SAH patients. However, at this point, discrepant findings in variable study settings, as well as timing and other issues, e.g., defining proper clinical endpoints (i.e., secondary clinical deterioration vs. angiographic vasospasm vs. secondary vasospastic infarct) do not allow for its routine use. It is also tempting to speculate about potential therapeutic measures targeting elevated IL-6 CSF levels and neuroinflammation in SAH patients. Corticosteroids and anti-platelet drugs are indeed used in many SAH cases (not necessarily with the intention to interfere with detrimental inflammatory signaling), however, no convincing benefit has been demonstrated yet. The lack of a robust clinical perspective against the background of a relatively large body of data linking IL-6 and neuroinflammation with the pathophysiology of SAH is somewhat disappointing. One underlying reason might be that most relevant studies only report correlative data. The specific molecular pathways behind elevated IL-6 levels in SAH patients and their various interactions still remain to be delineated. We are optimistic that future research in this field will result in a better understanding of the role of neuroinflammation in the pathophysiology of SAH, which in turn, will translate into the identification of suitable biomarkers and even potential therapeutic targets.     

脑卒中血浆脂肪酸及其代谢产物的UPLC-MS分析

脑卒中是一类高致残率、高死亡率的脑血管疾病,分为缺血性脑卒中和出血性脑卒中2种亚型,二者具有相似的临床症状,但治疗策略完全不同.目前,主要依赖医学影像学技术进行诊断,但存在耗时、费用高、难以区分2种脑卒中亚型等缺点,进而影响疾病治疗和预后.本研究收集了59例健康志愿者、60例急性脑缺血和36例脑出血患者的血浆样本,运用...     

Genetics and Epigenetics of Spontaneous Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a complex and heterogeneous disease, and there is no effective treatment. Spontaneous ICH represents the final manifestation of different types of cerebral small vessel disease, usually categorized as: lobar (mostly related to cerebral amyloid angiopathy) and nonlobar (hypertension-related vasculopathy) ICH. Accurate phenotyping aims to reflect these biological differences in the underlying mechanisms and has been demonstrated to be crucial to the success of genetic studies in this field. This review summarizes how current knowledge on genetics and epigenetics of this devastating stroke subtype are contributing to improve the understanding of ICH pathophysiology and their potential role in developing therapeutic strategies.     

临床护理路径在脑出血患者护理中的应用

目的 探讨临床护理路径在脑出血患者中的应用价值.方法 选取120例脑出血患者为研究对象,将其按不同的护理方法分为2组.观察组（n=60）采用临床护理路径进行护理,对照组（n=60）采用传统的护理模式进行护理,观察2组患者对护理的满意度及相关临床指标.结果 观察组在技术质量安全、服务及时、健康教育、人文关怀、服务态度、出入院教育等方面满意度明显优于对照组（P＜0.01）;观察组患者住院时间、住院费用、并发症发生率均明显少于对照组（P＜0.01）;出院后3个月观察组FIM评分和Fugl-Meyer评分明显高于对照组（P＜0.01）.结论 临床护理路径在脑出血护理中是一种有效的护理模式,可以有效提高患者满意度和临床疗效.     

Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway

Toll-like receptor 4 (TLR4) has been proven to play a critical role in neuroinflammation and to represent an important therapeutic target following subarachnoid hemorrhage (SAH). Resveratrol (RSV), a natural occurring polyphenolic compound, has a powerful anti-inflammatory property. However, the underlying molecular mechanisms of RSV in protecting against early brain injury (EBI) after SAH remain obscure. The purpose of this study was to investigate the effects of RSV on the TLR4-related inflammatory signaling pathway and EBI in rats after SAH. A prechiasmatic cistern SAH model was used in our experiment. The expressions of TLR4, high-mobility group box 1 (HMGB1), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) were evaluated by Western blot and immunohistochemistry. The expressions of Iba-1 and pro-inflammatory cytokines in brain cortex were determined by Western blot, immunofluorescence staining, or enzyme-linked immunosorbent assay. Neural apoptosis, brain edema, and neurological function were further evaluated to investigate the development of EBI. We found that post-SAH treatment with RSV could markedly inhibit the expressions of TLR4, HMGB1, MyD88, and NF-κB. Meanwhile, RSV significantly reduced microglia activation, as well as inflammatory cytokines leading to the amelioration of neural apoptosis, brain edema, and neurological behavior impairment at 24 h after SAH. However, RSV treatment failed to alleviate brain edema and neurological deficits at 72 h after SAH. These results indicated that RSV treatment could alleviate EBI after SAH, at least in part, via inhibition of TLR4-mediated inflammatory signaling pathway.     

Neuroelectric Mechanisms of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

Delayed cerebral ischemia (DCI) remains a challenging but very important condition, because DCI is preventable and treatable for improving functional outcomes after aneurysmal subarachnoid hemorrhage (SAH). The pathologies underlying DCI are multifactorial. Classical approaches to DCI focus exclusively on preventing and treating the reduction of blood flow supply. However, recently, glutamate-mediated neuroelectric disruptions, such as excitotoxicity, cortical spreading depolarization and seizures, and epileptiform discharges, have been reported to occur in high frequencies in association with DCI development after SAH. Each of the neuroelectric disruptions can trigger the other, which augments metabolic demand. If increased metabolic demand exceeds the impaired blood supply, the mismatch leads to relative ischemia, resulting in DCI. The neuroelectric disruption also induces inverted vasoconstrictive neurovascular coupling in compromised brain tissues after SAH, causing DCI. Although glutamates and the receptors may play central roles in the development of excitotoxicity, cortical spreading ischemia and epileptic activity-related events, more studies are needed to clarify the pathophysiology and to develop novel therapeutic strategies for preventing or treating neuroelectric disruption-related DCI after SAH. This article reviews the recent advancement in research on neuroelectric disruption after SAH.     

The Effect of Minimally Invasive Hematoma Aspiration on the JNK Signal Transduction Pathway after Experimental Intracerebral Hemorrhage in Rats

Objective: To explore the effect of minimally invasive hematoma aspiration (MIHA) on the c-Jun NH₂-terminal kinase (JNK) signal transduction pathway after intracerebral hemorrhage (ICH). Methods: In this experiment, 300 adult male Wistar rats were randomly and averagely divided into sham-operated group, ICH group and MIHA group. In each group, 60 rats were used in the detection of indexes in this experiment, while the other 40 rats were used to replace rats which reached the exclusion criteria (accidental death or operation failure). In ICH group and MIHA group, ICH was induced by injection of 70 µL of autologous arterial blood into rat brain, while only the rats in MIHA group were treated by MIHA 6 h after ICH. Rats in sham-operated group were injected nothing into brains, and they were not treated either, like rats in ICH group. In each group, six rats were randomly selected to observe their Bederson’s scales persistently (6, 24, 48, 72, 96, 120 h after ICH). According to the time they were sacrificed, the remaining rats in each group were divided into 3 subgroups (24, 72, 120 h). The change of brain water content (BWC) was measured by the wet weight to dry weight ratio method. The morphology of neurons in cortex was observed by the hematoxylin–eosin (HE) staining. The expressions of phospho-c-Jun NH₂-terminal kinase (pJNK) and JNK in peri-hematomal brain tissue were determined by the immunohistochemistry (IHC) and Western blotting (WB). Results: At all time points, compared with the ICH groups, the expression of pJNK decreased obviously in MIHA groups (p < 0.05), while their Bederson’s scales and BWC declined, and neuron injury in the cortex was relieved. The expression level of JNK was not altered at different groups. The data obtained by IHC and WB indicated a high-level of consistency, which provided a certain dependability of the test results. Conclusion: The JNK signal transduction pathway could be activated after intracerebral hemorrhage, with the expressions of pJNK increasing. MIHA could relieve the histo-pathological damage of nerve cells, reducing brain edema and neurological deficits, and these neuroprotective effects might be associated with suppression of JNK signal transduction pathway.     

脑出血后肺组织炎症损伤情况的研究

目的研究脑出血后肺组织炎症损伤的发病机制。方法用病理学常规HE染色法观察脑出血组和对照组肺标本的出血、渗出和炎症细胞浸润改变情况,在光镜下对白细胞、巨噬细胞进行记数。结果与对照组比较,脑出血组肺组织存在明显渗出、出血及大量白细胞、巨噬细胞浸润,炎症细胞记数有显著意义P<0.05。结论脑出血可以通过引发炎症反应导致急性肺损伤;炎症反应在3~5d时最明显。     

ERK介导的AQP4对脑出血后早期脑水肿的影响

目的探讨大鼠实验性脑出血后细胞外信号调节激酶（ERK）介导的水通道蛋白4（AQP4）的不同表达对早期脑水肿的影响。方法72只健康雄性大鼠随机分为出血组、PD98029组、截体溶液对照组和假手术组,每组各18只。采用大鼠缓慢注射自体血出血模型,测定脑组织含水量及伊文斯蓝含量,并采用免疫组织化学、Western blot检测AQP4的表达,测定预先经尾静脉给予PD98059后的丝裂原活化蛋白激酶（MAPKs）信号通路关键蛋白酶ERK1／2磷酸化水平,同时观察PD98059对AQP4和脑水肿的影响。结果假手术组AQP4表达较低;在出血组AQP4表达升高,脑组织含水量及伊文斯蓝含量增加;给予PD98059后AQP4的表达和脑组织含水量降低,同时ERK1／2磷酸化水平降低。结论出血性损伤后AQP4表达上升,脑水肿明显,早期预先给予PD98059可抑制AQP4的表达,降低BBB通透性,减轻脑水肿。     

冰冻灾害及其他心理因素对脑出血发病的影响

目的探讨冰冻灾害及其他社会心理因素对脑出血患者发病的影响。方法应用自制一般情况量表、生活事件量表、社会支持量表、特质应对方式问卷、A型行为类型评定量表对60例脑出血患者及60例健康体检者进行病例对照研究。结果冰冻灾害、文化、职业、高血压病史、糖尿病病史、卒中家族史、正性事件刺激量、负性事件刺激量、事件刺激总量、主观支持、对支持的利用度、消极应对、积极应对,脑出血患者与健康体检者比较差异有统计学意义（P〈0.05或P〈0.01）。多元逐步Logistic回归分析发现：冰冻灾害、高血压病史、负性事件刺激量与脑出血呈正相关（P〈0.05或P〈0.01）,主观支持与脑出血呈负相关（P〈0.05）。结论冰冻灾害作为社会环境因素对脑出血患者发病有明显影响。