Hamasaki Mike Yoshio, Barbeiro Hermes Vieira, Barbeiro Denise Frediani, Cunha Débora Maria Gomes, Koike Marcia Kiyomi, Machado Marcel Cerqueira César, Pinheiro da Silva Fabiano
Emergency Medicine Department, University of São Paulo, São Paulo, Brazil.
Emergency Medicine Department, University of São Paulo, São Paulo, Brazil.
J Neuroimmunol. 2016 Jan 15;290:33-5. doi: 10.1016/j.jneuroim.2015.11.014. Epub 2015 Nov 18.
Delirium, or acute confusional state, is a common manifestation in diseases that originate outside the central nervous system, affecting 30-40% of elderly hospitalized patients and up to 80% of the critically ill, even though it remains unclear if severe systemic inflammation is able or not to induce cellular disturbances and immune activation in the brain. Neuropeptides are pleotropic molecules heterogeneously distributed throughout the brain and possess a wide spectrum of functions, including regulation of the inflammatory response, so we hypothesized that they would be the major alarm system in the brain before overt microglia activation. In order to investigate this hypothesis, we induced acute pancreatitis in 8-10week old rats and collected brain tissue, 12 and 24h following pancreatic injury, to measure neuropeptide and cytokine tissue levels. We found significantly higher levels of β-endorphin, orexin and oxytocin in the brain of rats submitted to pancreatic injury, when compared to healthy controls. Interestingly, these differences were not associated with increased local cytokine levels, putting in evidence that neuropeptide release occurred independently of microglia activation and may be a pivotal alarm system to initiate neurologic reactions to distant inflammatory non-infectious aggression.
谵妄，即急性意识模糊状态，是起源于中枢神经系统以外疾病的常见表现，影响30% - 40%的老年住院患者，在危重症患者中这一比例高达80%，尽管目前尚不清楚严重的全身炎症是否能够在大脑中诱发细胞紊乱和免疫激活。神经肽是广泛分布于全脑的多效性分子，具有广泛的功能，包括调节炎症反应，因此我们推测它们可能是大脑中在小胶质细胞明显激活之前的主要警报系统。为了验证这一假设，我们在8 - 10周龄的大鼠中诱导急性胰腺炎，并在胰腺损伤后12小时和24小时收集脑组织，以测量神经肽和细胞因子的组织水平。与健康对照组相比，我们发现遭受胰腺损伤的大鼠大脑中β - 内啡肽、食欲素和催产素水平显著升高。有趣的是，这些差异与局部细胞因子水平升高无关，这表明神经肽的释放独立于小胶质细胞激活而发生，并且可能是启动对远处炎症性非感染性攻击的神经反应的关键警报系统。
