Lennart Levi Stress and Neuroimmunology Laboratory, Department of Pharmacology, School of Medicine and Nursing, University of Santiago de Compostela,C/San Francisco, s/n.15782 Santiago de Compostela, Spain.
Pharmacol Biochem Behav. 2010 Dec;97(2):350-6. doi: 10.1016/j.pbb.2010.09.002. Epub 2010 Sep 15.
The progression and development of multiple sclerosis (MS) has long been hypothesized to be associated with stress. Benzodiazepines have been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on their effects on MS, or experimental autoimmune encephalomyelitis (EAE), a model for human MS. We designed experiments conducted to ascertain whether alprazolam could modify the clinical, histological and neuroendocrine manifestations of acute EAE in Lewis rats exposed to a chronic auditory stressor. EAE was induced by injection of an emulsion of MBP and complete Freund's adjuvant containing Mycobacterium tuberculosis H37Ra. Stress application and treatment with drugs (placebo or alprazolam) were initiated 5days before inoculation and continued daily for the duration of the experiment (days 14 or 34 postinoculation).Our results show significant increases in the severity of neurological signs, the histological lesions of the spinal cord (inflammation), and the corticosterone plasmatic levels in stressed rats compared to those non-stressed ones. Treatment with alprazolam reversed the adverse effects of stress. These findings could have clinical implications in patients suffering from MS treated with benzodiazepines, so besides the psychopharmacological properties of alprazolam against stress, it has beneficial consequences on EAE.
多发性硬化症（MS）的进展和发展长期以来一直被假设与压力有关。在实验和临床模型中，苯二氮䓬类药物已被观察到可减轻压力对免疫系统的负面影响，但关于它们对 MS 或实验性自身免疫性脑脊髓炎（EAE）的影响（MS 的人类模型）没有数据。我们设计了实验，以确定在接触慢性听觉应激源的 Lewis 大鼠中，阿普唑仑是否可以改变急性 EAE 的临床、组织学和神经内分泌表现。通过注射含有结核分枝杆菌 H37Ra 的 MBP 和完全弗氏佐剂乳剂诱导 EAE。应激应用和药物（安慰剂或阿普唑仑）治疗在接种前 5 天开始，并在实验期间（接种后 14 或 34 天）每天持续进行。我们的结果表明，与非应激组相比，应激组大鼠的神经体征严重程度、脊髓组织学病变（炎症）和皮质酮血浆水平显著增加。用阿普唑仑治疗可逆转应激的不良影响。这些发现可能对接受苯二氮䓬类药物治疗的 MS 患者具有临床意义，因此除了阿普唑仑对压力的精神药理学特性外，它对 EAE 还有有益的影响。
