PMID- 37924484 OWN - NLM STAT- MEDLINE DCOM- 20240424 LR - 20240507 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 61 IP - 5 DP - 2024 May TI - Cerebrospinal Fluid from Patients After Craniotomy with the Appearance of Interleukin-6 Storm Can Activate Microglia to Damage the Hypothalamic Neurons in Mice. PG - 2707-2718 LID - 10.1007/s12035-023-03693-1 [doi] AB - We monitored CSF (cerebrospinal fluid) for Th1/Th2 inflammatory cytokines in a patient with unexplained postoperative disturbance of consciousness after craniotomy and found that the level of IL-6 (interleukin-6) concentrations was extremely high, meeting the traditional criteria for an inflammatory cytokine storm. Subsequently, the cerebrospinal fluid specimens of several patients were tested, and it was found that IL-6 levels were increased in different degrees after craniotomy. Previous studies have focused more on mild and long-term IL-6 elevation, but less on the effects of this short-term IL-6 inflammatory cytokine storm. Cerebrospinal fluid rich in IL-6 may play a significant role in patients after craniotomy. The objective is to explore the degree of IL-6 elevation and the incidence of IL-6 inflammatory cytokine storm in patients after craniotomy, as well as the effect of IL-6 elevation on the brain. In this study, the levels and clinical manifestations of inflammatory factors in cerebrospinal fluid after craniotomy were statistically classified, and the underlying mechanisms were discussed preliminarily. CSF specimens of patients after craniotomy were collected, IL-6 level was measured at 1, 5, and 10 days after operation, and cognitive function was analyzed at 1, 10, and 180 days after surgery. Craniotomy mouse model, cerebrospinal fluid of patients with the appearance of IL-6 storm after craniotomy, and IL-6 at the same concentration stimulation model were established. Behavioral tests, fluorescence in situ hybridization (FISH), pathological means, western blot, and ELISA (enzyme-linked immune-sorbent assay) were performed for verification. CSF from patients after craniotomy caused disturbance of consciousness in mice, affected neuronal damage in the hypothalamus, activation of microglia in the hypothalamus, and decreased expression of barrier proteins in the hypothalamus and brain. The large amount of interleukin-6 in CSF after craniotomy was found to be mainly derived from astrocytes. The IL-6 level in CSF after craniotomy correlated inversely with patients' performance in MoCA test. High levels of IL-6 in the cerebrospinal fluid derived from astrocytes after craniotomy may lead to disruption of the brain-cerebrospinal fluid barrier, most notably around the hypothalamus, which might result in inflammatory activation of microglia to damage the hypothalamic neurons and impaired cognitive function/more gradual cognitive repairment in patients after craniotomy with the appearance of IL-6 storm. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Huang, Haorun AU - Huang H AD - Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, China. FAU - Liao, Xixian AU - Liao X AD - Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, China. FAU - Zhang, An AU - Zhang A AD - Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, China. FAU - Qiu, Binghui AU - Qiu B AD - Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, China. FAU - Mei, Fen AU - Mei F AD - Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, China. FAU - Liu, Fan AU - Liu F AD - Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, China. FAU - Zeng, Kai AU - Zeng K AD - The First Clinical College, Southern Medical University, Guangzhou City, Guangdong Province, China. FAU - Yang, Chunen AU - Yang C AD - The First Clinical College, Southern Medical University, Guangzhou City, Guangdong Province, China. FAU - Ma, Haidie AU - Ma H AD - The First Clinical College, Southern Medical University, Guangzhou City, Guangdong Province, China. FAU - Ding, Wenjie AU - Ding W AD - The First Clinical College, Southern Medical University, Guangzhou City, Guangdong Province, China. FAU - Qi, Songtao AU - Qi S AD - Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, China. qisongtaonfyy@126.com. FAU - Bao, Yun AU - Bao Y AUID- ORCID: 0000-0002-5442-7363 AD - Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou City, Guangdong Province, China. 417406158@qq.com. LA - eng GR - 2021A1515111147/Province natural science fund of Guangdong/ GR - B2018245/Medical Scientific Research Foundation of Guangdong Province of China/ GR - 2018CR029/Clinical Research Program of Nafang Hospital, Southern Medical University/ GR - LC2016PY012，LC2019ZD004/Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education/ GR - 2018C017/President Foundation of Nanfang Hospital, Southern Medical University/ PT - Journal Article DEP - 20231104 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Interleukin-6) SB - IM MH - Adult MH - Aged MH - Animals MH - Female MH - Humans MH - Male MH - Mice MH - Middle Aged MH - *Craniotomy/adverse effects MH - *Hypothalamus/metabolism/pathology MH - *Interleukin-6/cerebrospinal fluid/metabolism MH - Mice, Inbred C57BL MH - Microglia/metabolism/pathology MH - Neurons/metabolism/pathology OTO - NOTNLM OT - Cerebrospinal fluid OT - Cognitive function OT - Craniotomy OT - Hypothalamic injury OT - IL-6 storm OT - Inflammation EDAT- 2023/11/04 21:51 MHDA- 2024/04/24 19:05 CRDT- 2023/11/04 12:11 PHST- 2023/03/11 00:00 [received] PHST- 2023/10/04 00:00 [accepted] PHST- 2024/04/24 19:05 [medline] PHST- 2023/11/04 21:51 [pubmed] PHST- 2023/11/04 12:11 [entrez] AID - 10.1007/s12035-023-03693-1 [pii] AID - 10.1007/s12035-023-03693-1 [doi] PST - ppublish SO - Mol Neurobiol. 2024 May;61(5):2707-2718. doi: 10.1007/s12035-023-03693-1. Epub 2023 Nov 4.