Peripheral osmotic stimulation inhibits the brain's innate immune response to microdialysis of acidic perfusion fluid adjacent to supraoptic nucleus.
Peripheral osmotic stimulation inhibits the brain's innate immune response to microdialysis of acidic perfusion fluid adjacent to supraoptic nucleus.
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DOI：
10.1152/ajpregu.00340.2009
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发表时间：
2009-11
期刊：
影响因子：
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通讯作者：
J. Summy-Long;Sanmei Hu
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文献类型：
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作者：
J. Summy-Long;Sanmei Hu
在大脑的先天免疫反应过程中，小胶质细胞、星形胶质细胞和室管膜细胞会解决/修复受损组织并控制感染。释放的白细胞介素-1β (IL-1β) 到达脑室刺激室周器官 (CVO；穹窿下器官，SFO；终板血管器官，OVLT)、正中视前核 (MePO) 以及视上核 (SON) 和室旁核 (PVN) 中的大细胞和细小细胞神经元。高渗盐水 (HS) 也会激活这些渗透感觉 CVO 和神经内分泌系统，但与 IL-1β 不同，它会抑制外周免疫反应。为了检查大脑的先天免疫反应是否因渗透刺激而减弱，在清醒大鼠的SON区域微透析（2微升/分钟）无菌酸性灌注液6小时，并在5小时时皮下注射无菌HS（1.5 M NaCl）（15 ml/kg）。免疫组织化学鉴定了探头附近、CVO、MePO、室管膜细胞、室周下丘脑、SON 和 PVN 中的细胞因子来源（IL-1beta(+)；OX-42(+) 小胶质细胞）和靶点（IL-1R(+)；诱导型环氧合酶、COX-2(+)；c-Fos(+)）。插入探针通过 MePO (c-Fos(+)) 刺激大细胞神经元 (c-Fos(+); SON; PVN)，HS 增强了这种反应。微透析激活邻近 SON 和双侧 PVN、室周下丘脑和室管膜血管周围区域的小胶质细胞（OX-42（+）；变形虫/肥大；IL-1beta（+）），与室管膜细胞中的 c-Fos 表达和脉管系统中的 COX-2 一致。这些小胶质细胞反应被 HS 减弱，同时激活小细胞和大细胞神经内分泌系统并升高循环 IL-1β、催产素和加压素。微透析引起的酸中毒引起的细胞损伤通过外周渗透刺激抑制的机制激活了大脑的先天免疫反应。
During the brain's innate immune response microglia, astroglia and ependymal cells resolve/repair damaged tissue and control infection. Released interleukin-1beta (IL-1beta) reaching cerebroventricles stimulates circumventricular organs (CVOs; subfornical organ, SFO; organum vasculosum lamina terminalis, OVLT), the median preoptic nucleus (MePO), and magnocellular and parvocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei. Hypertonic saline (HS) also activates these osmosensory CVOs and neuroendocrine systems, but, in contrast to IL-1beta, inhibits the peripheral immune response. To examine whether the brain's innate immune response is attenuated by osmotic stimulation, sterile acidic perfusion fluid was microdialyzed (2 microl/min) in the SON area of conscious rats for 6 h with sterile HS (1.5 M NaCl) injected subcutaneously (15 ml/kg) at 5 h. Immunohistochemistry identified cytokine sources (IL-1beta(+); OX-42(+) microglia) and targets (IL-1R(+); inducible cyclooxygenase, COX-2(+); c-Fos(+)) near the probe, in CVOs, MePO, ependymal cells, periventricular hypothalamus, SON, and PVN. Inserting the probe stimulated magnocellular neurons (c-Fos(+); SON; PVN) via the MePO (c-Fos(+)), a response enhanced by HS. Microdialysis activated microglia (OX-42(+); amoeboid/hypertrophied; IL-1beta(+)) in the adjacent SON and bilaterally in perivascular areas of the PVN, periventricular hypothalamus and ependyma, coincident with c-Fos expression in ependymal cells and COX-2 in the vasculature. These microglial responses were attenuated by HS, coincident with activating parvocellular and magnocellular neuroendocrine systems and elevating circulating IL-1beta, oxytocin, and vasopressin. Acidosis-induced cellular injury from microdialysis activated the brain's innate immune response by a mechanism inhibited by peripheral osmotic stimulation.