Sil Susmita, Ghosh Tusharkanti, Ghosh Rupsa
a Department of Physiology , University College of Science and Technology, University of Calcutta , Kolkata , India.
J Immunotoxicol. 2016 Jul;13(4):474-89. doi: 10.3109/1547691X.2015.1130760. Epub 2016 Jan 20.
The neurodegeneration in intracerebroventricular (icv) colchicine injected (ICIR) rats is linked with neuroinflammation. Glutamate excitotoxicity through NMDA receptors is involved with the neuroinflammation in some animal models of Alzheimer Disease (AD), but it has not been explored in ICIR rats. The aim of this study was to investigate the role of NMDA receptors (by blocking it's activity with memantine) in colchicine-induced neuroinflammation and neurodegeneration and impacts on peripheral immune parameters in ICIR rats. Levels of inflammatory markers (IL-1β, TNFα, ROS, nitrite) in the hippocampus and serum, histopathology of the hippocampus and select peripheral immune parameters were measured 14 and 21-days after icv colchicine injection in rats. These parameters were also measured in rats that received daily per os administration of memantine (20 mg/kg) in both study durations. Neuroinflammation in the hippocampus of ICIR rats was associated with neurodegeneration (chromatolysis, plaque formation), along with changes in inflammatory markers in the serum and alterations in peripheral immune parameters (phagocytic activity of WBC and splenic PMN, cytotoxic activity/leukocyte adhesion inhibition by splenic MNC). Administration of memantine to ICIR rats resulted in mitigation of colchicine-induced inflammation in the hippocampus, inflammatory markers in the serum and neurodegeneration and also led to recovery of the measured immune endpoints; most of these effects were greater with the longer duration of study. Phagocytic activity of WBC and splenic PMN cells appeared to correlate with levels of the measured central inflammatory markers. It appears from the results that neuroinflammation might be linked with the NMDA receptor activity in ICIR rats and that this receptor is involved in the process of progressive neuroinflammation and neurodegeneration in the hippocampus of ICIR and potentially in immunomodulation in these same hosts.
脑室内注射秋水仙碱（ICIR）的大鼠的神经退行性变与神经炎症有关。在一些阿尔茨海默病（AD）动物模型中，通过N-甲基-D-天冬氨酸（NMDA）受体的谷氨酸兴奋性毒性与神经炎症有关，但在ICIR大鼠中尚未进行研究。本研究的目的是探讨NMDA受体（通过美金刚阻断其活性）在秋水仙碱诱导的神经炎症和神经退行性变中的作用，以及对ICIR大鼠外周免疫参数的影响。在大鼠脑室内注射秋水仙碱后14天和21天，测量海马和血清中炎症标志物（白细胞介素-1β、肿瘤坏死因子α、活性氧、亚硝酸盐）的水平、海马的组织病理学以及选定的外周免疫参数。在两个研究阶段，还对每日口服美金刚（20mg/kg）的大鼠进行了这些参数的测量。ICIR大鼠海马中的神经炎症与神经退行性变（染色质溶解、斑块形成）有关，同时血清中炎症标志物发生变化，外周免疫参数也发生改变（白细胞和脾多形核白细胞的吞噬活性、脾单核细胞的细胞毒性活性/白细胞粘附抑制）。给ICIR大鼠服用美金刚可减轻秋水仙碱诱导的海马炎症、血清中的炎症标志物和神经退行性变，还可使所测免疫指标恢复；随着研究时间延长，这些作用大多更明显。白细胞和脾多形核白细胞的吞噬活性似乎与所测中枢炎症标志物的水平相关。从结果来看，神经炎症可能与ICIR大鼠的NMDA受体活性有关，且该受体参与ICIR大鼠海马中进行性神经炎症和神经退行性变过程，可能还参与这些宿主的免疫调节。
