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大鼠边缘系统损伤后外周血自然杀伤细胞的细胞毒性

Peripheral blood natural killer cell cytotoxicity after damage to the limbic system in the rat.

作者信息

Jurkowski M, Trojniar W, Borman A, Ciepielewski Z, Siemion D, Tokarski J

机构信息

Department of Animal Physiology, University of Gdańsk, Poland.

出版信息

Brain Behav Immun. 2001 Mar;15(1):93-113. doi: 10.1006/brbi.2000.0602.

DOI:10.1006/brbi.2000.0602
PMID:11259084
Abstract

The present work was aimed at examining the possible involvement of different parts of the septal area (dorsal, medial, lateral, and septohypothalamic nucleus), the basolateral amygdala, and the bed nucleus of the stria terminalis (BNST) in the regulation of the cytotoxic activity of NK cells (NKCC). The experimental approach included performing electrolytic (or sham) lesions in the tested brain areas and to measuring the peripheral blood NKCC (chromium-51 release assay), the number of leukocytes and lymphocytes, and the plasma corticosterone levels both before and at different time points after the lesion. Lesions were also induced in the three extralimbic structures: the paraventricular hypothalamic nucleus (PVN), the dorsal caudate-putamen, and the cerebellum. To test for a possible effect on NKCC of stress associated with blood collection, anesthesia, cranial surgery, and passing electric current through the brain the proper control experiments were also performed. Lesions of the medial septum and BNST caused gradual depression of NKCC, which peaked on the 10th day after the lesion, followed by a recovery to the baseline on days 21 (medial septum) and 42 (BNST) postinjury. In the respective sham-lesioned groups, mere insertion of electrodes into the medial septum and BNST evoked transient enhancement of NKCC (on the 3rd postlesion day), probably resulting from mechanical stimulation of the nervous tissue. Destruction of the other limbic and extralimbic structures appeared ineffective. After PVN lesions NKCC remained unchanged, despite an approximately 60% decrease in the basal corticosterone level. No adverse effects of the experimental and surgical procedures on NKCC, leukocyte and lymphocyte number, and corticosterone level were found, indicating that electrolytic lesions and other stereotaxic techniques can be safely used to study the brain-immune system interactions. The results obtained raise the question about the interrelationship between the medial septum and the hippocampal formation, BNST, the medial amygdala, and the hypothalamus (both medial and lateral) as a possible circuit involved in the regulation of cellular immune functions.

摘要

本研究旨在探讨隔区不同部位(背侧、内侧、外侧及隔下丘脑核)、基底外侧杏仁核及终纹床核(BNST)在调节自然杀伤细胞(NK)细胞毒性活性(NKCC)中的可能作用。实验方法包括在受试脑区进行电解(或假手术)损伤,并在损伤前及损伤后不同时间点测量外周血NKCC(铬-51释放试验)、白细胞和淋巴细胞数量以及血浆皮质酮水平。还在三个边缘外结构中诱导损伤:室旁下丘脑核(PVN)、背侧尾状核-壳核和小脑。为了测试采血、麻醉、开颅手术以及通过大脑施加电流所带来的应激对NKCC的可能影响,还进行了适当的对照实验。内侧隔区和BNST损伤导致NKCC逐渐降低,在损伤后第10天达到峰值,随后在损伤后第21天(内侧隔区)和第42天(BNST)恢复到基线水平。在各自的假手术损伤组中,仅将电极插入内侧隔区和BNST会引起NKCC短暂增强(在损伤后第3天),这可能是由于神经组织的机械刺激所致。破坏其他边缘和边缘外结构似乎无效。PVN损伤后,尽管基础皮质酮水平下降了约60%,但NKCC仍保持不变。未发现实验和手术操作对NKCC、白细胞和淋巴细胞数量以及皮质酮水平有不良影响,这表明电解损伤和其他立体定向技术可安全用于研究脑-免疫系统相互作用。所获得的结果提出了关于内侧隔区与海马结构、BNST、内侧杏仁核以及下丘脑(内侧和外侧)之间相互关系的问题,它们可能是参与调节细胞免疫功能的一个回路。

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