Surgery upregulates high mobility group box-1 and disrupts the blood-brain barrier causing cognitive dysfunction in aged rats.

CNS Neurosci Ther. 2012 Dec;18(12):994-1002. doi: 10.1111/cns.12018. Epub 2012 Oct 19. He HJ, Wang Y, Le Y, Duan KM, Yan XB, Liao Q, Liao Y, Tong JB, Terrando N, Ouyang W. In this paper, suggested by Dr Mueller, the authors looked at how general anesthesia (e.g. isoflurane) can disrupt the blood brain barrier, and lead to expression of HMGB1, a protein involved in regulation of transcription that is believed to be involved in neuroinflamation. To test the idea that anesthesia and surgery cause changes associated with neuroinflamation, rats were anesthetized with isoflurane and some underwent splenectomy. Results: Anesthesia alone did not increase systemic TNF-a or HMGB1, but anesthesia plus surgery did increase MHGB1 on the first postoperative day. When they looked at homogenized hippocampal protein and mRNA of IL-1B, TNF-a, HMGB1, and its receptor, RAGE, all were increased by anesthesia and anesthesia plus surgery. Surgery caused the changes to be significant at 1 and 3 days post-op. They also saw that anesthesia alone was sufficient to cause ruptures to the blood brain barrier, as evidenced by IgG leakage from blood vessels in to parenchyma. This leakage was even worse at 1 and 3 days post-op. In terms of cognition, rats treated with anesthesia or anesthesia and surgery both performed worse than control in a Morris water maze test. So I guess this is something we might want to keep in mind with our rats that get repeatedly imaged for longitudinal MRI studies, and also those who also undergo survival surgery. While this paper didn’t look at changes in the RVLM, it’s reasonable to think that they might occur at the same time the changes are happening in the hippocampus. -DH