Pasternak K I, Timo-Iaria C, Rodrigues C J, Maria D A, Duarte A J, Paiva L, Pozzi D H, de Mendonça B B, Wong M L, Licinio J
Clinical Neuroendocrinology Branch, National Institute of Mental Health, NIH, Bethesda, MD 20892-1284, USA.
Mol Psychiatry. 1998 Sep;3(5):397-404. doi: 10.1038/sj.mp.4000426.
Interactions between the immune system and the brain are a key element in the pathophysiology of diseases such as multiple sclerosis, neuroAIDS, and Alzheimer's, which affect large numbers of individuals and are associated with a high social cost. However, the neuroanatomical basis of brain-immune interactions has not been elucidated. We report that in Wistar rats of either sex bilateral electrolytic lesion of the medial forebrain bundle reduces body weight by 28% 7 days after lesioning, and causes widespread infections, aphagia, adypsia, structural damage to the lymphoid organs and heavy depression of T lymphocytes cytotoxicity. The following alterations occur in the immune system after those lesions: the weight of the thymus, spleen and lymphonodes is reduced by 77.9%, 49.1% and 48.4%, respectively. The thymus is atrophied and contains fewer lymphoid cells in the cortex than in the medulla. In the spleen the white pulp is reduced and lymphoid cells from periarteriolar zones and at the chords are almost absent. In lymph nodes cortical small lymphocytes are depleted and primary and secondary nodules and germinal centers all but disappear. Cytotoxicity of lymphocytes is reduced by 86.2% in the thymus, 77.6% in the spleen and 70.2% in lymph nodes. The critical area of lesion is at the medialmost portion of the medial forebrain bundle, at the preoptic area and rostral part of the anterior hypothalamus. We suggest that this area contains neural circuits that are crucial for keeping the structure of lymphoid organs and the functional integrity of the immune system.
免疫系统与大脑之间的相互作用是诸如多发性硬化症、神经艾滋病和阿尔茨海默病等疾病病理生理学的关键要素,这些疾病影响着大量个体并带来高昂的社会成本。然而,大脑 - 免疫相互作用的神经解剖学基础尚未阐明。我们报告称,在雌雄Wistar大鼠中,内侧前脑束的双侧电解损伤在损伤后7天可使体重减轻28%,并导致广泛感染、拒食、拒饮、淋巴器官结构损伤以及T淋巴细胞细胞毒性严重降低。这些损伤后免疫系统会出现以下改变:胸腺、脾脏和淋巴结的重量分别减少77.9%、49.1%和48.4%。胸腺萎缩,皮质中的淋巴细胞比髓质中的少。脾脏中白髓减少,动脉周围区域和弦状组织处的淋巴细胞几乎消失。淋巴结中皮质小淋巴细胞减少,初级和次级结节以及生发中心几乎消失。胸腺中淋巴细胞的细胞毒性降低86.2%,脾脏中降低77.6%,淋巴结中降低70.2%。损伤的关键区域在内侧前脑束的最内侧部分、视前区和下丘脑前部的 Rostral 部分。我们认为该区域包含对维持淋巴器官结构和免疫系统功能完整性至关重要的神经回路。