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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.

american journal of physiology. regulatory, integrative and comparative physiology/american journal of physiology. regulatory, integrative, and comparative physiology

Peripheral osmotic stimulation inhibits the brain's innate immune response to microdialysis of acidic perfusion fluid adjacent to supraoptic nucleus