title: Toll-like receptor 4 (TLR4) is correlated with delayed cerebral ischemia (DCI) and poor prognosis in aneurysmal subarachnoid hemorrhage.
abstract: Toll-like receptor 4 (TLR4) is one of key players in regulation of inflammation. Animal experiments have suggested an important role of TLR4 in the pathophysiology of subarachnoid hemorrhage (SAH). In present study, TLR4 is investigated in clinical SAH patients to explore its clinical significance. 30 patients with aneurysmal subarachnoid hemorrhage (aSAH) and 20 healthy control patients (HC) were enrolled in this prospective study. Blood samples were collected on days 1, 3 and 7 after admission. TLR4 expression level on cell surface of peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry and presented as mean fluorescence intensity (MFI). Patients were clinically assessed every day after admission to monitor the occurrence of delayed cerebral ischemia (DCI). Participants were followed up until completion of 3 months after SAH. Functional outcome was defined by modified Rankin score (mRs). Results show that SAH patients presented a significantly higher TLR4 levels on days 1 and 3 post SAH compared to HC; TLR4 levels in SAH patients on day 1 was highest compared with that on days 3 and 7 and in HC. TLR4 of SAH patients on day 7 declined to the level showing no significant difference with that of HC. In patients with Hunt-Hess grades I-III lower TLR4 levels were observed. Patients with DCI showed significantly higher TLR4 levels than those without DCI. High TLR4 levels were statistically significantly associated with poor functional outcome after 3 months. Logistic regression analysis showed that TLR4 level on day 1 was independent predictor for DCI and 3-month poor neurological outcome of aneurysmal SAH patients. In summary, admission TLR4 level on PBMCs (day 1) is an independent risk factor to predict the occurrence of DCI and 3-month poor neurological outcome in aneurysmal SAH patients.
authors.affiliation: Department of Neurosurgery, Henan Provincial People's Hospital, Zhengzhou 450003, China. Electronic address: machunxiao148@163.com.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Zhaoyue
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Mingqi
authors.initials: M
authors.lastname: Qu
authors.affiliation: Department of Neurosurgery, Henan Provincial People's Hospital, Zhengzhou 450003, China.
authors.forename: Xingyao
authors.initials: X
authors.lastname: Bu
mesh_terms: D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000097:blood*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015600:Glasgow Coma Scale; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D013345:Subarachnoid Hemorrhage / Q000097:blood*; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000097:blood*; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: Aneurysmal subarachnoid hemorrhage (aSAH); Delayed cerebral ischemia (DCI); Interleukin-6 (IL-6); Peripheral blood mononuclear cells (PBMCs); Poor clinical outcome; Toll-like receptor 4 (TLR4); Tumor necrosis factor-α (TNF-α)