化痰通络汤对脑缺血/再灌注大鼠“肠-脑”轴的干预作用

目的 基于“肠-脑”轴探讨化痰通络汤（HTTLD）对大鼠脑缺血再灌注后脑组织和肠道形态和功能的影响。方法 将60只SPF级雄性大鼠随机分为假手术组，模型组，HTTLD高、中、低剂量组（28.66，14.33，7.16 g·kg^-1），依达拉奉（4 g·kg^-1）+丁酸梭菌（5.0×10⁸ cfu·mL^-1）组，采用大鼠局灶性脑缺血再灌注模型，灌胃给药HTTLD，神经功能缺损评分和2，3，5-氯化三苯四氮唑（TTC）染色法测定脑组织损伤，小肠推进率观察脑缺血再灌注对肠道动力的影响，十二指肠黏膜的病理形态学检测评价肠黏膜细胞损伤，酶联免疫吸附测定法（ELISA）测定血清D-乳酸（D-LAC），二胺氧化酶（DAO），细菌内毒素（LPS）含量，蛋白免疫印迹法（Western blot）检测十二指肠的闭合蛋白（Occludin），紧密连接蛋白-5（Claudin-5），闭锁小带蛋白-1（ZO-1）蛋白的表达。结果 脑缺血再灌注后，大鼠出现神经功能缺损症状，与假手术组比较，模型组神经功能缺损评分显著升高（P<0.01）；与模型组比较，HTTLD中、高剂量组能显著减少神经功能缺损症状，降低神经功能缺损评分（P<0.01）。与假手术组比较，模型组大鼠脑组织出现明显梗死灶，脑梗死率显著升高（P<0.01）；与模型组比较，各给药组脑梗死体积明显减少（P<0.01），以HTTLD高剂量组的效应最佳，且效应具有剂量依赖性。小肠推进率结果显示，与假手术组比较，模型组小肠推进率显著降低（P<0.01）；与模型组比较，各给药组能显著升高小肠推进率（P<0.01），以HTTLD高剂量效应最佳，且效应具有剂量依赖性。十二指肠黏膜组织病理学检测显示，脑缺血再灌注后十二指肠黏膜可见明显损伤，各给药组黏膜损伤情况明显减轻。与假手术组比较，模型组ZO-1，Occludin，Claudin-5蛋白表达均显著降低（P<0.01）；与模型组比较，HTTLD低、中、高剂量组能不同程度上调ZO-1，Occludin，Claudin-5蛋白表达（P<0.05，P<0.01），以高剂量组的效应最为显著。与假手术组比较，模型组血清D-LAC，DAO，LPS蛋白含量均显著升高（P<0.01）；与模型组比较，各给药组D-LAC，DAO含量均明显降低（P<0.05，P<0.01），HTTLD中、高剂量组明显降低LPS含量（P<0.05，P<0.01），且HTTLD高剂量组的作用最明显。结论 脑缺血再灌注后，大鼠脑组织受损、出现神经功能障碍，同时肠道黏膜损伤、肠道蠕动减弱和肠道黏膜屏障破坏。HTTLD能减少脑组织和胃肠道黏膜损伤，减轻神经功能缺损症状，提高胃肠道动力、改善肠道屏障功能、减少肠道细菌代谢产物和毒物的释放，从而发挥对脑缺血再灌注后“脑-肠”轴损伤的保护作用。     

Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver

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Therapeutic ultrasound: The future of epilepsy surgery?

Epilepsy is one of the leading neurological diseases in both adults and children and in spite of advancement in medical treatment, 20 to 30% of patients remain refractory to current medical treatment. Medically intractable epilepsy has a real impact on a patient's quality of life, neurologic morbidity and even mortality. Actual therapy options are an increase in drug dosage, radiosurgery, resective surgery and non-resective neuromodulatory treatments (deep brain stimulation, vagus nerve stimulation). Resective, thermoablative or neuromodulatory surgery in the treatment of epilepsy are invasive procedures, sometimes requiring long stay-in for the patients, risks of permanent neurological deficit, general anesthesia and other potential surgery-related complications such as a hemorrhage or an infection. Radiosurgical approaches can trigger radiation necrosis, brain oedema and transient worsening of epilepsy. With technology-driven developments and pursuit of minimally invasive neurosurgery, transcranial MR-guided focused ultrasound has become a valuable treatment for neurological diseases. In this critical review, we aim to give the reader a better understanding of current advancement for ultrasound in the treatment of epilepsy. By outlining the current understanding gained from both preclinical and clinical studies, this article explores the different mechanisms and potential applications (thermoablation, blood brain barrier disruption for drug delivery, neuromodulation and cortical stimulation) of high and low intensity ultrasound and compares the various possibilities available to patients with intractable epilepsy. Technical limitations of therapeutic ultrasound for epilepsy surgery are also detailed and discussed.     

Blood-brain barrier integrity in the pathogenesis of Alzheimer’s disease

The blood–brain barrier (BBB) tightly controls the molecular exchange between the brain parenchyma and blood. Accumulated evidence from transgenic animal Alzheimer’s disease (AD) models and human AD patients have demonstrated that BBB dysfunction is a major player in AD pathology. In this review, we discuss the role of the BBB in maintaining brain integrity and how this is mediated by crosstalk between BBB-associated cells within the neurovascular unit (NVU). We then discuss the role of the NVU, in particular its endothelial cell, pericyte, and glial cell constituents, in AD pathogenesis. The effect of substances released by the neuroendocrine system in modulating BBB function and AD pathogenesis is also discussed. We perform a systematic review of currently available AD treatments specifically targeting pericytes and BBB glial cells. In summary, this review provides a comprehensive overview of BBB dysfunction in AD and a new perspective on the development of therapeutics for AD.