雌激素对脑出血后继发性损伤的作用

脑出血是一种高发病率和高死亡率的疾病,出血后继发性脑水肿、神经细胞毒性损伤、血肿周围的炎性反应等可引起一系列继发性损伤,并导致严重后果,但目前尚缺乏能明显减轻脑出血后继发性损伤的治疗措施。近年来,较多研究发现雌激素在脑出血后能减轻红细胞溶解产物及铁离子的神经细胞毒性反应、脑血管痉挛及继发性炎性反应,从而发挥神经保护作用。进一步深入研究雌激素在脑出血后的作用机理,对于指导脑出血病人的治疗具有重大意义。     

炎症反应在脑出血后继发性脑损伤中作用机制的研究进展

正脑出血是第二大卒中类型,病死率和致残率高~([1])。目前,脑出血仍然没有统一规范的确切治疗方法。脑出血引起脑损伤的机制仍然不清楚,许多研究表明炎症反应在脑出血继发性脑损伤过程中有重要作用,调控炎症反应有助于减轻继发性脑损伤、脑水肿,改善神经功能障碍~([2,3])。本文就炎症反应在脑     

小胶质细胞激活与脑出血后继发性脑损伤机制的研究进展

最近研究发现,小胶质细胞激活参与了脑出血后的继发性损伤。激活的小胶质细胞大量分泌促炎性因子、基质金属蛋白酶和血红素加氧酶-1等,这些物质加重了脑出血后的炎症反应和氧化应激,导致明显的脑水肿和神经功能障碍。应用药物抑制小胶质细胞激活,减少上述物质的表达,明显减轻了脑出血大鼠的脑水肿和提高了行为学评分。本文对小胶质细胞激活参与脑出血继发性损伤的机制作一综述,以期为脑出血的治疗提供新的思路。     

microRNAs在脑出血后病理生理机制中的作用

脑出血是一种高发病率和高死亡率的疾病,出血后的一系列继发性反应可以造成的严重的神经功能损伤.近年来,研究发现多个microRNA在脑出血后异常表达,参与了出血后的氧化损伤、炎症、水肿以及神经细胞凋亡等多个病理生理过程,从而加重了脑出血后继发性脑损伤.本文综述了目前microRNAs在脑出血后病理生理机制中作用的相关研究.     

脑出血后继发海马神经元损伤的机制研究进展

脑出血是一种致死率、致残率较高的疾病,除造成血肿周围损伤外,还可致远端脑区损伤及其功能发生变化,例如脑出血可致海马结构和功能发生改变,包括神经细胞坏死、突触可塑性破坏,炎症因子表达增加,谷氨酸大量释放,以及N-甲基-D-天冬氨酸受体（NMDAR）过度激活等。海马神经元损伤与脑出血后继发性损伤机制相关,目前脑出血后继发性损伤机制存在多种说法,如谷氨酸兴奋性毒性、自噬激活、炎症、氧化应激以及铁超载等。这些机制的研究为脑出血后海马神经元损伤所致认知功能障碍的治疗奠定相关理论基础,推动脑出血后认知障碍治疗的发展。     

脑出血后凝血酶的神经毒性研究进展

脑出血(intracerebral hemorrhage,ICH)是神经科常见的急、危、重症之一,有较高的病死率和致残率。脑出血后除血肿扩大导致的机械性损伤外,还有脑水肿、细胞凋亡、炎症反应、脑血管痉挛等继发性损伤[1]。研究表明凝血酶是导致脑出血后继发性损伤的重要因素。本文就凝血酶及其神经毒性、抗凝治疗展望做一综述。     

出血性脑损伤细胞凋亡机制研究进展

近年研究认为 :出血性脑损伤以继发性损伤为主 ,细胞凋亡机制参与了脑出血继发性损伤。脑出血导致细胞凋亡可能与出血后凝血酶大量形成、红细胞分解产物聚集、兴奋性氨基酸受体激活、多种细胞因子释放及炎细胞浸润等因素有关。探讨脑出血细胞凋亡机制可能为防治出血性脑损伤寻找到新的靶点     

依达拉奉治疗高血压急性脑出血的临床疗效观察

脑出血(ICH)后脑损伤病理过程中,脑水肿是脑出血后神经元受第二次打击的中心环节,也是脑出血后继发性脑损伤的主要标志.自由基损伤是主要的机制之一.依达拉奉是一种强效的羟自由基清除剂,可抑制脂质过氧化反应引起的神经细胞损伤,提高缺血神经元的生存能力,为观察依达拉奉对急性脑出血的疗效,设立了治疗组和对照组. 1 对象与方法     

脑出血后血肿周围组织炎症反应的研究进展

脑出血是临床常见的血管性疾病,发病率、死亡率和致残率都较高,但目前尚缺乏能明显改善预后的治疗措施。脑出血后继发性脑损伤的机制较复杂,其中血肿周围组织炎症反应在继发性脑损伤中发挥重要作用。研究发现,炎症细胞的渗出及浸润、细胞因子的上调、基质金属蛋白酶的释放以及活性氧的过度产生等多种因素均参与血肿周围组织炎症反应。进一步深入研究脑出血后血肿周围组织炎症反应及其可调节性,对指导临床脑出血病人的治疗具有重大意义。     

脑出血损伤相关分子模式研究进展

脑出血后产生的免疫风暴可导致神经元及其支持细胞死亡,红细胞裂解释放的血红蛋白、血红素和铁离子等细胞毒性物质也具有促进神经细胞死亡的作用。神经细胞死亡后释放的损伤相关分子模式(DAMP)激活固有免疫反应,导致炎症反应-细胞死亡-DAMP释放-炎症反应的恶性循环,是脑出血后继发性脑损伤的重要机制。本文旨在对目前开展的一系列探讨DAMP在脑出血继发性脑损伤中作用的研究进展进行概述,以为进一步的基础研究与临床转化研究提供参考。     

小鼠脑出血后不同时间点小胶质细胞极化状态的实验研究

目的 观察小鼠脑出血后不同时间点小胶质细胞M1及M2型的转化，为促炎型M1型小胶质细胞向抗
炎修复型M2型小胶质细胞的转化，减轻脑出血后神经功能损伤提供理论依据。
方法 选取健康雄性ICR小鼠48只，随机分为假手术组、脑出血组，每组按术后时间点不同随机
分为1 d、3 d、7 d三个时间点，每个时间点8只。通过立体定位仪用微量注射器向尾状核注射Ⅳ型胶
原酶0.5 U制备脑出血模型，假手术组注射等量生理盐水。各组于术后对应时间点参照改良Garcia
评分量表进行神经功能缺损评分后灌注取脑，采用蛋白免疫印迹检测M1型小胶质细胞标志物肿瘤
坏死因子α（tumor necrosis factor-α，TNF-α）、白细胞介素6（interleukin-6，IL-6），M2型小胶质细胞
标志物脑源性神经营养因子（brai n-derived neurotrophic factor，BDNF）、胰岛素样生长因子1（insulinlike
growth factor 1，IGF-1）的含量；采用免疫荧光染色标记小胶质细胞M1型（Iba1+CD80）、M2型
（Iba1+CD206），评价出血后血肿周围组织小胶质细胞活化状态。
结果 脑出血组1 d、3 d、7 d各时间点Garci a评分均较假手术组低，TNF-α、IL-6、BDNF及I GF-1的蛋白
表达量均较假手术组增多（均P＜0.01）。脑出血后1 d时M1型高于M2型小胶质细胞数量（38.33±1.53
vs 23.00±3.00，P =0.01）；3 d时M1型同样高于M2型（66.33±3.06 vs 57.33±2.52，P =0.02）；7 d时M1
型低于M2型（33.67±1.15 vs 52.33±0.58，P＜0.01）。
结论 脑出血急性期（1～3 d）以M1型小胶质细胞为主，脑出血亚急性期（7 d）以M2型小胶质细胞
为主。     

Molecular pathophysiology of cerebral hemorrhage: secondary brain injury

Intracerebral hemorrhage (ICH) is an often fatal type of stroke that kills approximately 30,000 people annually in the United States. If the patient survives the ictus, then the resulting hematoma within brain parenchyma triggers a series of adverse events causing secondary insults and severe neurological deficits. This article discusses selected aspects of secondary brain injury after ICH and outlines key mechanisms associated with hematoma toxicity, oxidative stress, and inflammation. Finally, this review discusses the relevance of hematoma resolution processes as a target for ICH therapy and presents potential clinically relevant molecular targets that could be harnessed to treat secondary injury associated with ICH injury.     

Potential Application of Intranasal Insulin Delivery for Treatment of Intracerebral Hemorrhage: A Review of The Literature

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke associated with high morbidity and mortality that is considered a medical emergency, mainly managed with adequate blood pressure control and creating a favorable hemostatic condition. However, to date, none of the randomized clinical trials have led to an effective treatment for ICH. It is vital to better understand the mechanisms underlying brain injury to effectively decrease ICH-associated morbidity and mortality. It is well known that initial hematoma formation and its expansion have detrimental consequences. The literature has recently focused on other pathological processes, including oxidative stress, neuroinflammation, blood-brain barrier disruption, edema formation, and neurotoxicity, that constitute secondary brain injury. Since conventional management has failed to improve clinical outcomes significantly, various neuroprotective therapies are tested in preclinical and clinical settings. Unlike intravenous administration, intranasal insulin can reach a higher concentration in the cerebrospinal fluid without causing systemic side effects. Intranasal insulin delivery has been introduced as a novel neuroprotective agent for certain neurological diseases, including ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury. Since there is an overlap of mechanisms causing neuroinflammation in these neurological diseases and ICH, we believe that preclinical studies testing the role of intranasal insulin therapy in ICH are warranted.     

Acute inflammatory reaction following experimental intracerebral hemorrhage in rat

Previous studies on intracerebral hemorrhage (ICH) indicate that brain edema increases progressively in the first 24 h and remains elevated for several days. The cause of secondary brain injury and edema formation is uncertain. We hypothesized that inflammatory mediators released from the blood after cerebral hemorrhage might cause secondary brain injury and edema formation. This study investigates if, when and where inflammation occurs after ICH in rat. Immunocytochemistry for polymorphonuclear leukocyte marker (myeloperoxidase, MPO), microglia marker (OX42) and intracellular adhesion molecule-1 (ICAM-1) was performed in control, and 1, 3, 7 and 10 days after the injection of 100 microliter autologous blood in the right basal ganglia. Double labeling immunohistochemistry was used to identify ICAM-1 positive cells. The results show that an inflammatory response occurred in and around the blood clot after ICH, characterized by the infiltration of neutrophils and macrophages as well as activation of microglia. ICAM-1 immunoreactivity was observed in blood vessels adjacent to the clot, as well as in activated microglia and neurons in the ipsilateral hemisphere. The present study demonstrates there is an inflammatory response in the brain after ICH. Infiltrating leukocytes and activated microglia may release cytotoxic mediators contributing to secondary brain injury.     

干细胞移植治疗脑出血的关键影响因素研究进展

近年脑出血的干细胞治疗策略因其良好的前景吸引了越来越多基础和临床研究工作者 的兴趣。临床前研究表明移植诸如胚胎干细胞、诱导多能干细胞、神经干细胞和间充质干细胞等均 可获得不错的疗效,并揭示了脑出血后干细胞移植治疗起效的可能机制有细胞替代、神经营养与保 护、促血管生成、免疫炎症反应调节等。尽管临床研究也表明干细胞治疗脑出血安全有效,但影响干 细胞移植治疗的几大关键因素尚未确定,例如移植的细胞类型、细胞数量、移植时间、最佳给药途径、 最佳受众人群以及如何追踪细胞等。本文根据最新研究成果就以上关键影响因素的研究进展作一 综述,为后续研究提供有价值的参考。     

The complement cascade as a therapeutic target in intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is the second most common and deadliest form of stroke. Currently, no pharmacologic treatment strategies exist for this devastating disease. Following the initial mechanical injury suffered at hemorrhage onset, secondary brain injury proceeds through both direct cellular injury and inflammatory cascades, which trigger infiltration of granulocytes and monocytes, activation of microglia, and disruption of the blood–brain barrier with resulting cerebral edema. The complement cascade has been shown to play a central role in the pathogenesis of secondary injury following ICH, although the specific mechanisms responsible for the proximal activation of complement remain incompletely understood. Cerebral injury following cleavage of complement component 3 (C3) proceeds through parallel but interrelated pathways of anaphylatoxin-mediated inflammation and direct toxicity secondary to membrane attack complex-driven erythrocyte lysis. Complement activation also likely plays an important physiologic role in recovery following ICH. As such, a detailed understanding of the variation in functional effects of complement activation over time is critical to exploiting this target as an exciting translational strategy for intracerebral hemorrhage.     

家犬实验陛脑出血后血肿周围脑代谢的微透析监测

目的研究脑出血（intracerebral hemorrhage,ICH）后继发脑损伤的机制。方法雄性成年家犬12只,随机分为ICH组（n=6）和生理盐水对照组（n=6）,ICH组于额叶注入非抗凝自体动脉血,对照组动物在相同部位注入等量生理盐水。在模型制备后2h、6h、24h、3d、7d、14d进行血肿周围脑组织间液微透析,监测葡萄糖、乳酸、丙酮酸、甘油和谷氨酸浓度。结果ICH组葡萄糖浓度无显著变化;乳酸浓度在注血后24h和3d升高;丙酮酸浓度在注血后6h、24h和3d升高;甘油浓度在注血后24h升高：谷氨酸浓度在注血后升高,3d达到高峰,至14d明显高于对照组和基础值。结论ICH后血肿周围脑组织代谢变化提示存在“生化半暗带”区域,兴奋性氨基酸的聚集可能是加重和维持继发性脑损伤的重要因素。     

神经炎症在动脉瘤性蛛网膜下腔出血后早期脑损伤中的作用

早期脑损伤(early brain injury,EBI)是影响动脉瘤性蛛网膜下腔出血(aneurysmal subarachnoid hemorrhage,aSAH)患者预后的重要因素之一.目前aSAH后EBI产生机制尚不明确,神经炎症可能为其主要驱动因素,其作用机制包括:红细胞降解产物和激活的小胶质细胞诱导神经炎症...