自发性蛛网膜下腔出血后早期脑损伤机制研究进展

自发性蛛网膜下腔出血（SAH）是高病死率和病残率的三大脑血管疾病之一,影响自发性SAH患者预后的主要因素是早期脑损伤和血管痉挛等并发症。有学者认为早期脑损伤（EBI）是影响自发性SAH患者预后的主要因素。本研究就近年来国内外学者在自发性SAH后EBI病理机制的研究进展作一综述。     

蛛网膜下腔出血后脑微循环障碍在缺血性脑损伤中的作用

近年来,尽管动脉瘤性蛛网膜下腔出血(subarachnoid hemorrhage,SAH)的治疗取得了长足进步,但其病死率和致残率并未得到有效控制.SAH后缺血性脑损伤被认为是患者预后不良的重要原因,但其发生机制尚未完全阐明.研究表明,SAH后脑微循环障碍与缺血性脑损伤的发生密切相关.文章就SAH后脑微循环障碍与缺血性脑损伤的研究进展进行了综述.     

内质网应激在蛛网膜下腔出血后早期脑损伤中的作用

自发性蛛网膜下腔出血(subarachnoid hemorrhage,SAH)是临床上的一种急性脑血管病,致残率和病死率均很高.最近的研究显示,SAH发病后72 h内即会出现早期脑损伤(early braininjury,EBI),并与SAH患者转归不良密切相关.导致EBI的可能机制有许多,例如炎症、自噬、细胞凋亡等,这些损伤机制均与内质网应激有关.文章就内质网应激在SAH后EBI中的作用进行了综述.     

蛛网膜下腔出血后早期免疫炎性损伤与自身保护机制的研究进展

蛛网膜下腔出血(SAH)是临床常见的脑血管疾病之一,具有发病急、病死率高、预后差等临床特点。传统观念认为,SAH后继发脑血管痉挛(cerebral vasospasm,CVS),是导致缺血性脑损伤的主要机制。随着现代分子生物学研究的不断深入,研究人员更加注重SAH后早期脑损伤的研究,主要集中在炎性介质与细胞因子"级联瀑布",微循环灌注与利用间的矛盾,神经内分泌与自身脑保护及皮质神     

Caspase-3抑制剂对蛛网膜下腔出血后早期脑损伤的作用

目的 探讨Caspase-3抑制剂在蛛网膜下腔出血后早期脑损伤中的作用.方法 颈内动脉穿刺制作大鼠蛛网膜下腔出血模型.将大鼠随机分成3组:实验组(38只)模型制作后腹腔注射Caspase-3抑制剂 Z-VAD-FMK(10 μmol/L,0.3 mL);对照组(38只)注射等体积二甲基亚砜(DMSO);正常组(16只)未进行任何处理.72 h记录死亡率、神经功能评分、脑水肿、血脑屏障通透性等脑损伤指标;TUNEL染色检测神经元细胞凋亡,免疫组化、Western Blot检测Caspase-3表达.结果 Caspase-3抑制剂可降低大鼠死亡率(47.4%vs28.9%,P<0.05),减轻脑水肿,保护血脑屏障,减少Caspase-3蛋白表达及神经元细胞凋亡(P<0.05),但对神经功能评分无明显影响(P>0.05).结论 细胞凋亡在SAH后早期脑损伤中起重要作用,可减轻SAH后早期脑损伤.     

自噬在蛛网膜下腔出血后早期脑损伤中作用的研究进展

近几年研究发现,蛛网膜下腔出血（SAH）后72 h内即出现的早期脑损伤（early brain injury,EBI）与SAH的不良预后密切相关,成为研究关注的热点.自噬（autophagy）很早就被发现存在于多种组织细胞中,参与降解和回收受损细胞器和大分子物质,出现于多种生理过程和疾病的病理过程中.Lee 等[1]研究发现,SAH后立即可检测到皮质内自噬活性的增强.但自噬在SAH后EBI中的作用及具体机制尚不明确.我们就自噬与EBI的关系综述如下.     

蛛网膜下腔出血并发症患者的护理

蛛网膜下腔出血（SAH）是由于脑底部或脑表面血管破裂，大量血液流入蛛网膜下腔的急性出血性脑血管疾病。SAH起病急，进展快，病情多变，早期监测、预防SAH的并发症。可有效地降低患者病死率和致残率。因此，护理工作极为重要，现将58例SAH的护理体会报告如下。     

动脉瘤性蛛网膜下腔出血患者急性期外周血中高迁移率族蛋白1水平的变化

颅内动脉瘤破裂导致的自发性蛛网膜下腔出血(SAH)发生后的最初72h内,机体会发生多种病理改变。近年来,这些早期出现的急性病理改变逐渐被学者们所重视,并被认为可能是影响预后的重要因素[1]。在SAH引起的早期脑损伤中,神经炎性反应被视为引起早期病理变化的因素之一。高迁移率族蛋白1(high-mobility group box protein-1,HMGB-1)是一种普遍存在于哺乳动物细胞中的核蛋白,能调     

法舒地尔对大鼠蛛网膜下腔出血早期脑损伤的行为能力及海马区神经细胞凋亡的影响

目的探讨法舒地尔对大鼠实验性蛛网膜下腔出血(SAH)早期脑损伤的行为能力及海马区神经细胞凋亡的影响。方法雄性成年健康SD大鼠随机分为假手术(sham)组、蛛网膜下腔出血(SAH)组、药物(Fasudil)组,每组各8只。颈内动脉刺破法建立大鼠SAH模型,各组干预后72 h穿梭箱实验测试大鼠行为能力,麻醉处死,海马区组织进行HE染色观察细胞形态,TUNEL染色观察凋亡细胞数量。结果对比sham组,SAH组逃避反应时间(ERT)延长,主动回避反应率(AARR)降低,海马区HE染色正常神经细胞较少,TUNEL染色表达细胞增多,差异均有统计学意义(均P0.05)。对比SAH组,Fasudil组ERT缩短,AARR升高,海马区HE染色正常神经细胞较多,TUNEL染色表达细胞减少,差异均有统计学意义(P0.05)。结论 SAH后大鼠行为能力较差,海马区神经细胞凋亡明显。法舒地尔可减轻早期脑损伤,减少神经细胞的凋亡,改善大鼠的行为能力。     

蛛网膜下腔出血后脑血管痉挛的危险因素

脑血管痉挛(CVS)是蛛网膜下腔出血(SAH)患者死亡和残疾的主要原因。CVS的发生率约为30%-60%,一般于SAH后3-4d开始出现症状,第2周达高峰,需3周左右恢复。早期评价病情和预测CVS的发生,有利于预防和恰当的治疗,降低病死率和致残率。文章对SAH后CVS的危险因素做了综述。     

Melatonin decreases mortality following severe subarachnoid hemorrhage

Abstract:  Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disease that is associated with significant morbidity and mortality. There is substantial evidence to suggest that oxidative stress is significant in the development of acute brain injury following SAH. Melatonin is a strong antioxidant that has low toxicity and easily passes through the blood–brain barrier. Previous studies have shown that melatonin provides neuroprotection in animal models of ischemic stroke. This study hypothesizes that melatonin will provide neuroprotection when administered 2 hr after SAH. The filament perforation model of SAH was performed in male Sprague–Dawley rats weighing between 300 and 380 g. Melatonin (15 or 150 mg/kg), or vehicle was given via intraperitoneal injection 2 hr after SAH. Mortality and neurologic deficits were assessed 24 hr after SAH. A significant reduction in 24-hr mortality was seen following treatment with high dose melatonin. There was no improvement in neurologic scores with treatment. Brain water content and lipid peroxidation were measured following the administration of high dose melatonin to identify a mechanism for the increased survival. High dose melatonin tended to reduce brain water content following SAH, but had no effect on the lipid peroxidation of brain samples. Large doses of melatonin significantly reduces mortality and brain water content in rats following SAH through a mechanism unrelated to oxidative stress.     

Melatonin attenuates inflammatory response‐induced brain edema in early brain injury following a subarachnoid hemorrhage: a possible role for the regulation of pro‐inflammatory cytokines

Melatonin is a strong anti‐oxidant that has beneficial effects against early brain injury (EBI) following a subarachnoid hemorrhage (SAH) in rats; protection includes the reduction of both mortality and neurological deficits. The molecular mechanisms underlying these clinical effects in the SAH model have not been clearly identified. This study examined the influence of melatonin on brain edema secondary to disruption of the blood–brain barrier (BBB) and the relationship between these effects and pro‐inflammatory cytokines in EBI following SAH using the filament perforation model of SAH in male Sprague–Dawley rats. Melatonin (150 mg/kg) or vehicle was given via an intraperitoneal injection 2 hr after SAH induction. Brain samples were extracted 24 hr after SAH. Melatonin treatment markedly attenuated brain edema secondary to BBB dysfunctions by preventing the disruption of tight junction protein expression (ZO‐1, occludin, and claudin‐5). Melatonin treatment also repressed cortical levels of pro‐inflammatory cytokines (IL‐1β, IL‐6, and TNF‐α), which were increased in EBI 24 hr after SAH. To further identify the mechanism of this protection, we demonstrated that administration of melatonin attenuated matrix metallopeptidase 9 expression/activity and vascular endothelial growth factor expression, which are related to the inflammatory response and BBB disruption in EBI after SAH. Taken together, this report shows that melatonin prevents disruption of tight junction proteins which might play a role in attenuating brain edema secondary to BBB dysfunctions by repressing the inflammatory response in EBI after SAH, possibly associated with regulation of pro‐inflammatory cytokines.     

Epidemiology of Traumatic Brain Injury and Subarachnoid Hemorrhage

Incidence rates of traumatic brain injury are high in both industrialized and non-industrialized countries and have been estimated variously to be between 150–250 cases per 100,000 population per year. The estimated incidence rates for subarachnoid hemorrhage (SAH) are between 10 to 25 cases per 100,000 population per year. Seasonal variation in the occurrence of subarachnoid hemorrhage has been reported in studies from different countries, with significant seasonal variations and peak periods for aneurysmal SAH differing widely. A differential racial distribution for SAH has been found as well as a higher mortality rate for women than for men. The cognitive and behavioral consequences of TBI and SAH are significant and affect the quality of life of patients and their families. Recent publications have informed of hypopituitary deficits in patients sustaining TBI or SAH. It is not clear whether the cognitive deficits found in these patients are due to the consequences of the brain injury itself or are related to the hypopituitary deficits. There is a need for research distinguishing the differential cognitive and behavioral effects of the brain injury and the endocrinological deficits in these patients, and for developing adequate treatment.     

Melatonin‐enhanced autophagy protects against neural apoptosis via a mitochondrial pathway in early brain injury following a subarachnoid hemorrhage

Melatonin is a strong antioxidant that has beneficial effects against early brain injury (EBI) following a subarachnoid hemorrhage (SAH) in rats; protection includes reduced mortality and brain water content. The molecular mechanisms underlying these clinical effects in the SAH model, however, have not been clearly identified. This study was undertaken to determine the influence of melatonin on neural apoptosis and the potential mechanism of these effects in EBI following SAH using the filament perforation model of SAH in male Sprague Dawley rats. Melatonin (150 mg/kg) or vehicle was given via an intraperitoneal injection 2 hr after SAH induction. Brain samples were extracted 24 hr after SAH. The results show that melatonin treatment markedly reduced caspase‐3 activity and the number of TUNEL‐positive cells, while the treatment increased the LC3‐II/LC3‐I, an autophagy marker, which indicated that melatonin‐enhanced autophagy ameliorated apoptotic cell death in rats subjected to SAH. To further identify the mechanism of autophagy protection, we demonstrated that melatonin administration reduced Bax translocation to the mitochondria and the release of cytochrome c into the cytosol. Taken together, this report demonstrates that melatonin improved the neurological outcome in rats by protecting against neural apoptosis after the induction of filament perforation SAH; moreover, the mechanism of these antiapoptosis effects was related to the enhancement of autophagy, which ameliorated cell apoptosis via a mitochondrial pathway.     

Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling

Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide‐binding oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti‐inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. This study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels, and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood–brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC), cleaved caspase‐1, interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6); these changes were also associated with an increase in the anti‐apoptotic factor (Bcl2) and reduction in the pro‐apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome‐associated apoptosis.     

Neurogenic cardiac injury

Opinion statement Cardiac injury may occur following many types of brain injury, although the most widely investigated form of neurocardiogenic injury is subarachnoid hemorrhage (SAH). Echocardiography may help prognosticate and aid in the treatment of SAH if left ventricular (LV) dysfunction is suspected or if troponin levels are elevated. Cardiac catheterization, however, is not routinely recommended in SAH patients with LV dysfunction and elevated troponin. The priority should be treatment of the underlying neurological condition, even in the setting of LV dysfunction. Cardiac injury that occurs following an SAH appears to be reversible. For patients that develop brain death cardiac evaluation under optimal conditions may help increase the donor pool.     

抑制ERK1/2可减轻蛛网膜下腔出血大鼠脑水肿和下调基质金属蛋白酶-9表达

目的 研究细胞外信号调节激酶1/2(extracellular signal-regulated kinase1/2,ERK1/2)通路抑制剂U0126对蛛网膜下腔出血(subarachnoid hemorrhage,SAH)大鼠脑组织基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9...     

脑红蛋白对蛛网膜下腔出血大鼠早期脑损伤的保护作用

目的探讨脑红蛋白（NGB）对蛛网膜下腔出血（SAH）大鼠早期脑损伤的保护作用。方法将60只清洁级sD大鼠随机分为4组：正常组、假手术组、SAH组、治疗组（SAH＋腹腔注射氯化血红素）组。除SAH组30只外,其余每组10只大鼠。采用枕大池单次注血法建立大鼠SAH模型。采用免疫组化法和图像分析技术观测SAH后,不同时间大脑皮质颞叶的NGB免疫组化反应及平均吸光度A值;采用干湿法测量脑含水量,原位细胞凋亡检测法（TUNEL）检测颞叶神经元凋亡情况。结果①正常组和SAH后24h组平均吸光度4值分别是0．133±0．021和0．236±0．028：②sAH后颞叶皮质NGB阳性反应细胞迅速增加,24h达高峰,随后逐渐减少;③SAH组脑含水量为（77．5±0．4）％,治疗组脑含水量为（76．5±0．6）％,治疗组脑含水量较SAH组减少,差异有统计学意义（P〈0．05）;④治疗组和SAH组脑颞叶神经元凋亡程度为（9．8±2．4）％、（18．5±2．3）％。治疗组脑皮质神经元凋亡程度较SAH组降低（P〈0．05）。结论SAH后大鼠大脑皮质NGB阳性反应细胞呈动态变化。早期给予NGB能减少大鼠SAH模型的皮质神经元凋亡,降低脑水肿程度,具有明显的脑保护作用。     

Remodelling of cerebrospinal fluid lipoproteins after subarachnoid hemorrhage

Lipoprotein particles (Lps) in normal human cerebrospinal fluid (CSF) are distinct from those found in plasma and include unique apolipoprotein E (apoE indicates protein; APOE, gene) containing lipoproteins rarely seen in human plasma. Less favourable neurological recovery after subarachnoid hemorrhage (SAH) has been observed in patients who possess the APOE epsilon4 allele raising the possibility that apoE influences neuronal survival after brain injury. We analysed Lps from control and SAH CSF testing the hypotheses that following brain injury CSF Lps undergo remodelling and apoE containing Lps are selectively depleted from brain injury CSF. Lipoproteins were fractionated using CSF from six control pools and six patients with SAH on a sepharose 6HR 10/30 size exclusion column. Fractions were assayed for total cholesterol (TC), free cholesterol (FC), phospholipid, triglyceride (TG), apoE, apolipoprotein B (apoB), and apolipoprotein AI (apoAI). Compared to control CSF there were significant (P<0.05) increases in TC, FC, TG, and apoAI in SAH CSF. Plasma sized apoB-containing lipoproteins and a very small apoAI-containing Lps were identified in the SAH CSF, which were not present in controls. However, despite the release of plasma lipoproteins into the subarachnoid space, there was no significant increase in CSF apoE. These data provide novel indirect evidence suggesting that after SAH CSF Lps undergo remodelling and apoE containing Lps are selectively reduced in brain injury CSF. The remodelling of CSF Lps and selective reduction of apoE containing lipoproteins may reflect an important response of the human brain to injury.