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41.
目的探讨黄芩苷对海人酸诱导的小鼠癫痫持续状态后海马组织x染色体连锁凋亡抑制蛋白(XIAP)表达的影响。方法将90只ICR雄性小鼠随机分为对照组、癫痫持续状态(sE)组、黄芩苷治疗组,每组30只;采用侧脑室注入海人酸建立小鼠癫痫持续状态模型。通过苏木素一伊红(HE)染色观察黄芩苷对小鼠癫痫持续状态后海马神经细胞的形态学改变;应用免疫组化和Westernblot方法检测小鼠海马组织中XIAP的表达量。结果黄芩苷明显改善sE后小鼠海马组织的病理形态学,海马CA3区XIAP在sE后6h起逐渐增加,12h达高峰,24h有所下降;与对照组比较,差异有统计学意义(P〈0.01)。黄芩苷治疗组海马XIAP蛋白表达在6h、12h和24h均高于sE组(P〈0.05)。结论黄芩苷对小鼠癫痫持续状态后海马神经细胞的保护作用,可能与其促进XIAP的表达有关。 相似文献
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Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35 °C using brain temperature as reference, and should be maintained at least during 48 hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1 °C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients. 相似文献
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Naomi K. Kleitman 《The journal of spinal cord medicine》2013,36(4):311-318
AbstractSummary: Centuries of medical wisdom-namely that spinal cord injury (SCI) treatmentwas limited to caretaking until the patients inevitably succumbed to complications-has given way to tremendous medical and research advancements. The prognosis for survival after SCI improved significantly after World War II, leading to the largest population of people aging with chronic SCI in history. Despite the general Iack of optimism for functional recovery after SCI, the spinal cord has proven to be one of the most attractive systems for studying central nervaus system plasticity. Predictions of clinical applications derived from basic findings now routinely accompany reports of evidence for spinal axon regeneration. This has led to great debate in the SCI research community about the Ievei and quality of evidence needed to select truly promising candidate therapies. This article reviews the basis for optimism in the new understanding of the processes of degeneration after SCI and the mechanisms of regeneration. The emphasis is on neuroprotective and reparative strategies ernerging from the animal literature, and on the steps remaining to be taken to translate these into effective clinical trials of new therapies. Examples of the translational process in related areas of brain injury and strake are cited, as weil as the specific issues relating to the needs of individuals with SCI. 相似文献
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外伤性视神经病变(TON)为头部或颅面部外伤的严重并发症之一,患者多为青壮年,是一种发病率不高但可导致严重视力减退的颅脑外伤并发性疾病,可对患者心理健康及社会适应性产生严重的不良影响。其发病机制尚未明确,临床上易延误确诊,且缺乏统一的治疗指导方案,各治疗手段临床治疗效果各异。本文通过查阅最新相关文献,对TON的病因及发病机制、诊断、治疗等方面的最新研究进展进行综述。 相似文献
46.
目的探讨骨化三醇对大鼠局灶性脑缺血-再灌注模型的保护效应及其机制。方法将54只健康雄性成年SD大鼠随机分为三组:假手术组(8只)、骨化三醇干预组(23只,2μg.k-g1.d-1,持续8 d)和安慰剂组(23只,脂肪乳剂2m l.kg-1.d-1,持续8 d)。在第8天给药结束后1 h,以线栓法制作大鼠右侧大脑中动脉缺血后1 h再灌注模型,检测其3、6、9 h新皮质核转录因子(NF-κB)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-10及72 h时脑梗死体积及神经细胞损伤情况。结果骨化三醇干预组与安慰剂组相比,脑缺血-再灌注后3、6、9 h的NF-κB活性、TNF-α含量亦显著降低(P<0.05),6 h的IL-10含量显著增加(P<0.05)。脑缺血-再灌注72 h骨化三醇组大鼠相对脑梗死体积为(11.8±3.6)%,明显小于安慰剂组的(21.6±4.2)%,P<0.05。结论骨化三醇可能通过对炎症介质的免疫调节减轻大鼠脑缺血-再灌注性损伤。 相似文献
47.
Mauro B. AlmeidaJosé Luiz Martins do Nascimento Anderson Manoel HerculanoMaria Elena Crespo-López 《Biomedicine & Pharmacotherapy》2011,65(4):239-243
Molecular chaperones (or heat shock proteins) are evolutionarily conserved and essential proteins that play a key role in cell survival through cytoprotective mechanisms. Despite their possible clinical applications, the understanding of these structures is still quite limited. The aim of the present study is to review the literature to understand the physiological importance, implication in various diseases (especially in cancer and neurodegenerative diseases), possible applicability, and future prospects of heat shock proteins. The cytoprotective mechanisms of molecular chaperones can be co-opted by oncogenic processes favoring tumor growth, invasion, evasion of apoptosis, and metastasis, thus making inhibitors to these molecules possible therapeutic options for cancer patients. However, there is also evidence showing that upregulation of heat shock proteins can have an antineoplastic effect through immunomodulatory activity. This is why chaperones have already been investigated for conventional chemotherapy under specific conditions, yielding interesting results. The induction of heat shock protein activity is also of potential benefit in many other diseases where structural and functional preservation of proteins may enhance cell survival, including neurodegeneration, trauma, stroke, and cardiovascular disease. In addition, the immune properties of chaperones can potentially be exploited for such diseases as diabetes, atherosclerosis, and other chronic inflammatory conditions. Thus, continuing efforts to clarify the role of chaperones may guide the development of new therapeutic modalities capable of minimizing the impact of diseases such as cancer, heart disease, and diabetes as well as obtaining better results in neurological conditions currently lacking alternative treatments. 相似文献
48.
Gael Barthet Julie Dunys Zhiping Shao Zhao XuanYimin Ren Jindong XuAnastasios Georgakopoulos Junichi ShioiNikolaos K. Robakis 《Neurobiology of aging》2013
Activation of EphB receptors by ephrinB (efnB) ligands on neuronal cell surface regulates important functions, including neurite outgrowth, axonal guidance, and synaptic plasticity. Here, we show that efnB rescues primary cortical neuronal cultures from necrotic cell death induced by glutamate excitotoxicity and that this function depends on EphB receptors. Importantly, the neuroprotective function of the efnB/EphB system depends on presenilin 1 (PS1), a protein that plays crucial roles in Alzheimer's disease (AD) neurodegeneration. Furthermore, absence of one PS1 allele results in significantly decreased neuroprotection, indicating that both PS1 alleles are necessary for full expression of the neuroprotective activity of the efnB/EphB system. We also show that the ability of brain-derived neurotrophic factor (BDNF) to protect neuronal cultures from glutamate-induced cell death depends on PS1. Neuroprotective functions of both efnB and BDNF, however, were independent of γ-secretase activity. Absence of PS1 decreases cell surface expression of neuronal TrkB and EphB2 without affecting total cellular levels of the receptors. Furthermore, PS1-knockout neurons show defective ligand-dependent internalization and decreased ligand-induced degradation of TrkB and Eph receptors. Our data show that PS1 mediates the neuroprotective activities of efnB and BDNF against excitotoxicity and regulates surface expression and ligand-induced metabolism of their cognate receptors. Together, our observations indicate that PS1 promotes neuronal survival by regulating neuroprotective functions of ligand-receptor systems. 相似文献
49.
目的:观察JAK2-STAT3信号转导通路在树鼩缺血后适应(ischemic postconditioning,IPoC)神经保护中的调控作用,探讨阻断JAK2-STAT3通路后脑损伤加重的机制。方法:通过光化学反应建立树鼩血栓性脑缺血模型;于缺血后4 h夹闭患侧颈总动脉3次(每次5 min)实施IPoC。于IPoC前10 min侧脑室注射AG490(JAK2抑制剂)后,采用TTC染色观察树鼩脑梗死面积的变化,通过HE染色和电镜观察脑皮层神经元形态改变及超微结构变化,应用Western blot检测IPoC及AG490处理后皮层t-STAT3和p-STAT3蛋白水平的变化。结果:缺血24 h,皮层神经元固缩,线粒体肿胀,嵴溶解;脑梗死面积占半脑面积的(24.78±3.30)%;此时皮层神经元STAT3磷酸化水平明显增高(P<0.01)。IPoC后皮层神经元损伤减轻,线粒体肿胀改善,脑梗死面积占半脑面积的百分比减小为(17.67±1.83)%(P<0.01),STAT3磷酸化水平进一步增高(P<0.01)。然而,给予AG490处理后,皮层神经元损伤加重,脑梗死面积再次增大为(23.85±2.77)%(P<0.05),STAT3磷酸化水平则明显降低(P<0.05)。结论:IPoC可能通过调控STAT3的磷酸化而减轻树鼩缺血性脑损伤,抑制JAK2-STAT3信号通路可抵消IPoC的保护效应而加重脑损伤。 相似文献
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