Postoperative cognitive dysfunction (POCD) is a common complication that presents in the postoperative stage, especially in elderly patients. Despite years of considerable progress, the detailed molecular mechanisms of POCD remain largely unknown. Neuroinflammation has been increasingly pointed out as one of the core mechanisms for the pathogenesis of POCD. However, application of anti-inflammatory drugs failed to show consistent beneficial effect in patients with cognitive decline. Hence, it might be of great importance to identify the inflammatory initiators that are involved in the mediation, amplification and perpetuation of postoperative neuroinflammatory reactions. Extracellular RNAs (exRNAs), released from necrotic cells, were demonstrated to initiate the inflammatory responses in various pathological conditions. Recent study has suggested neuroprotective and edema protective effects of ribonuclease (RNase), the counterpart of RNA, in acute stroke. It was theorized that RNase acted against endogenous RNA that was released from tissue damage. Similarly, we have observed significant attenuation of cognitive impairment by RNase in aged mice after unilateral nephrectomy. Damping the systemic initiators at early stages may help to prevent the chain reaction that triggers the central inflammatory or apoptotic response. Therefore, we propose the hypothesis that exRNAs released upon stress, through acting on the peripheral and/or central receptors, may trigger a damaging cascade leading to the development of POCD. Undoubtedly, further study is urgently needed to elucidated the exact signaling mechanisms and confirm the proposed hypothesis.
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