脑出血与细胞凋亡

近年来的研究表明，细胞凋亡是脑出血的继发性损伤机制之一。脑出血后细胞凋亡可能与出血后凝血酶大量释放、红细胞分解产物聚积、兴奋性氨基酸受体激活、多种细胞因子表达和炎性细胞浸润等有关，是一个复杂的病理生理学过程。干预这些病理生理学环节有可能抑制脑出血后细胞凋亡，并为防治出血后的继发性脑损伤找到一些新的途径。     

脑出血与细胞凋亡

近年来的研究表明,细胞凋亡是脑出血的继发性损伤机制之一。脑出血后细胞凋亡可能与出血后凝血酶大量释放、红细胞分解产物聚积、兴奋性氨基酸受体激活、多种细胞因子表达和炎性细胞浸润等有关,是一个复杂的病理生理学过程。干预这些病理生理学环节有可能抑制脑出血后细胞凋亡,并为防治出血后的继发性脑损伤找到一些新的途径。     

脑出血后继发性脑损伤机制研究进展

脑出血是具有高病死率和高致残率的神经科常见疾病。近年研究证实,脑出血发病过程中存在炎症反应、氧化应激、凝血酶神经毒性、小胶质细胞激活、细胞凋亡等继发性脑损伤机制,继发性脑损伤是导致脑出血后神经细胞损伤的重要因素。目前尚缺乏有效的治疗脑出血手段,研究脑出血后继发性脑损伤机制,为脑出血治疗提供一条新途径。     

核因子-κB在脑出血后继发性脑损伤中作用的研究进展

核因子-κB(NF-κB)是一种广泛存在于真核细胞内,能将信息从胞浆传至胞核引起相应基因表达的重要转录因子,在机体免疫和炎症反应、细胞凋亡等有关基因转录过程中具有重要的调控作用。脑出血诱导了NF-κB的激活,活化的NF-κB参与炎性反应、诱导细胞凋亡、介导自由基损伤等机制加重了脑出血后继发性脑损伤。NF-κB将为脑出血后继发性脑损伤的病理生理机制及治疗开辟新途径。     

炎症反应在脑出血后细胞凋亡中的作用

脑出血后血肿周围区可发生继发性损伤。最近的研究表明，血肿周围区出血后神经细胞的死亡，其中炎症反应在脑出血后细胞凋亡中起着十分重要的作用，包括白细胞和小胶质细胞渗出、多种细胞因子的表达以及基质金属蛋白酶和凝血酶的释放。对脑出血后炎症反应的作用进行研究，有望找到新的脑出血治疗的切入点。     

炎症反应在脑出血后细胞凋亡中的作用

脑出血后血肿周围区可发生继发性损伤。最近的研究表明,血肿周围区出血后神经细胞的死亡,其中炎症反应在脑出血后细胞凋亡中起着十分重要的作用,包括白细胞和小胶质细胞渗出、多种细胞因子的表达以及基质金属蛋白酶和凝血酶的释放。对脑出血后炎症反应的作用进行研究,有望找到新的脑出血治疗的切入点。     

脑出血后继发性脑损伤机制

脑出血后继发性脑损伤与脑水肿、炎症反应以及其他损伤因素,如补体系统激活、兴奋性氨基酸毒性、血管活性物质释放和自由基损伤等密切相关.脑出血后继发性脑损伤时的神经元死亡方式主要为坏死和凋亡.     

脑出血家兔模型血肿周围脑组织细胞凋亡与c-fos表达水平的关系

目的 探讨血肿周围脑组织细胞凋亡与c-fos mRNA及c-fos蛋白表达的关系及脑出血后继发性损伤的机制.方法 健康家兔42只,随机分为正常组6只,出血模型组36只,采用多种方法检测血肿周围组织中的凋亡细胞、c-fos mRNA、c-fos蛋白的表达.结果 与对照组相比,实验组出血后0.5h内可见凋亡细胞,逐渐增多,48 h到高峰;c-fos mRNA在脑出血后0.5h达到高峰,依次递减,24 h后就基本消失;c-fos蛋白表达则延后,在脑出血后半小时表达比较明显,2h达高峰,6h仍然较明显,随后递减.结论 脑出血后血肿周围的脑组织中细胞凋亡与c-fos相关,即早基因之一的c-fos可能对其具有调节作用.     

小胶质细胞在脑出血中的作用研究进展

脑出血是一种严重的中枢神经系统出血性损伤,出血后炎性反应在其发病后损害及修复中发挥重要作用。小胶质细胞是神经系统固有免疫细胞,脑出血后小胶质细胞激活,可分泌抗炎因子如白细胞介素10、神经生长因子-1及促炎因子白细胞介素1、肿瘤坏死因子α等,在脑出血继发损伤中起到促炎致损及抑炎修复的双向作用。调节小胶质细胞功能状态,增强其组织保护功能,可以促进脑出血后血肿清除,减弱炎性反应,减轻继发性损伤。作者就脑出血后小胶质细胞的激活与功能作用及相关分子机制进行综述,以期为脑出血治疗提供新思路。     

脑出血后神经细胞死亡机制的研究进展

正脑出血后血管内容物通过理化损伤机制,尤其血液成分所产生的大量细胞毒性因子造成神经细胞不同形式的死亡。研究显示,在人和动物脑出血标本中均发现了血肿周围组织存在坏死、凋亡、自噬、坏死性凋亡等神经细胞的多种死亡方式[1]。近年来,有研究报道铁死亡为小鼠脑出血模型中存在的新的细胞死亡方式[2-3]。由此可见,脑出血后继发性神经细胞死亡机制具有多样的生物学特性。本研究对脑出血后继发性神经细胞死亡方式的特点、调节机制、干预靶点等进行综述。     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.