摘要
Peripheral administration of the E. coli endotoxin lipopolysaccharide (LPS) to rats promotes secretion of pro-inflammatory cytokines and in previous studies was associated with transient enlargement of cortical volumes. Here, resiquimod (R848) was administered to mice to stimulate peripheral immune activation, and the effects on brain volumes and neurometabolites determined. After baseline scans, 24 male, wild-type C57BL mice were triaged into three groups including R848 at low (50 μg) and high (100 μg) doses and saline controls. Animals were scanned again at 3 h and 24 h following treatment. Sickness indices of elevated temperature and body weight loss were observed in all R848 animals. Animals that received 50 μg R848 exhibited decreases in hippocampal N-acetylaspartate and phosphocreatine at the 3 h time point that returned to baseline levels at 24 h. Animals that received the 100 μg R848 dose demonstrated transient, localized, volume expansion (~5%) detectable at 3 h in motor, somatosensory, and olfactory cortices; and pons. A metabolic response evident at the lower dose and a volumetric change at the higher dose suggests a temporal evolution of the effect wherein the neurochemical change is demonstrable earlier than neurostructural change. Transient volume expansion in response to peripheral immune stimulation corresponds with previous results and is consistent with brain swelling that may reflect CNS edema.
摘要译文
大肠杆菌内毒素脂多糖（LPS）对大鼠的外周给药可促进促炎性细胞因子的分泌，并且在先前的研究中，与皮质体积的短暂增大有关。在这里，对小鼠进行了重新启动（R848），以刺激外周免疫激活，并确定对脑体积和神经元代谢物的影响。基线扫描后，将24名男性野生型C57BL小鼠分为三组，包括低（50μg）和高（100μg）剂量和盐水对照组的R848。治疗后3小时和24小时再次扫描动物。在所有R848动物中，观察到温度升高和体重减轻的疾病指数。接受50μgR848的动物在海马N-乙酰天冬氨酸和磷酸甲酸酯的3小时时间点显示，在24小时后返回基线水平。接受100μgR848剂量的动物表现出在运动，体感和嗅觉皮质的3小时内检测到的瞬时，局部体积膨胀（约5％）；和pons。在较低剂量下明显的代谢反应和较高剂量时的体积变化表明，这种作用的时间演变，其中神经化学变化比神经结构的变化早已证明。响应于周围免疫刺激的瞬时体积扩展与先前的结果相对应，并且与可能反映CNS水肿的脑肿胀一致。
Natalie May Zahr;Qingyu Zhao;Ryan Goodcase;Adolf Pfefferbaum. Systemic Administration of the TLR7/8 Agonist Resiquimod (R848) to Mice Is Associated with Transient, In Vivo-Detectable Brain Swelling[J]. Biology, 2022,11(2): 274